Category Archives: Immunology

Immunology

Cancer immune cell: what have scientists discovered? – The Week UK

The discovery of a killer cell in the human immune system could lead to a one-size-fits-all cancer treatment, according to a newly published study.

The team of Cardiff University researchers who made the find say the T-cell has already been used in lab tests to attack and destroyprostate, breast, lung and other cancer cells.

Although no tests have been conducted yet on human patients, scientists say the findings - outlined in a newly publishedpaperin the journal Nature Immunology -haveenormous potential, the BBC reports.

One of the most groundbreaking advances in the fight against cancer in recent years is a treatment known as CAR-T immunotherapy. This therapy involves harvesting a patients immune T-cells and reprogramming them to target specific proteins found on the patients cancer cells, while leaving healthy cells undamaged, explains science news siteNew Atlas.

However, a major limitation facing researchers of CAR-T therapies has been the lack of a universal T-cell receptor (TCR) that can target different kinds of cancers in all patients.

But the T-cell discovered by the Welsh university team appears to be equipped with a new type of TCR that does exactly that.

This T-cell recognises a molecule present on the surface of a wide range of cancer cells, and normal cells, and is able to distinguish between healthy and cancerous cells - killing only the latter, The Independentreports.

In lab tests on mice and human cells, the T-cells equipped with the new TCR has been found to kill lung, skin, blood, colon, breast, bone, prostate, ovarian, kidney and cervical cancer cells.

If these sorts of effects can be replicated in humans,says ScienceAlert, we could be looking at a bright new future for T-cell treatments.

According to Wales Online, experiments are under way to determine the precise molecular mechanism by which the new TCR distinguishes between healthy cells and cancer, and researchers hope to begin human patients towards the end of this year following further safety testing.

Cardiff University professor Awen Gallimore, a cancer immunology lead for the Wales Cancer Research Centre, said: If this transformative new finding holds up, it will lay the foundation for a universal T-cell medicine, mitigating against the tremendous costs associated with the identification, generation and manufacture of personalised T-cells.

This is truly exciting and potentially a great step forward for the accessibility of cancer immunotherapy.

Alasdair Rankin of blood cancer charity Bloodwise added: This research represents a new way of targeting cancer cells that is really quite exciting, although much more research is needed to understand precisely how it works.

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Cancer immune cell: what have scientists discovered? - The Week UK

Immunology

Hairy cells in the nose called brush cells may be involved in causing allergies – Science News

Some hairy cells in the nose may triggersneezing and allergies to dust mites, mold and other substances, new work withmice suggests.

When exposed to allergens, these brushcells make chemicals that lead to inflammation, researchers report January17 in Science Immunology. Only immunecells previously were thought to make such inflammatory chemicals fattycompounds known as lipids. The findings may provide new clues about how peopledevelop allergies.

Brush cells are shaped like teardropstopped by tufts of hairlike projections. In people, mice and other animals, thesecells are also found in the linings of the trachea and the intestines, wherethey are known as tuftcells (SN: 4/13/18). However, brushcells are far more common in the nose than in other tissues, and may help thebody identify when pathogens or noxious chemicals have been inhaled, says LoraBankova, an allergist and immunologist at Brigham and Womens Hospital inBoston.

Bankova and her colleagues discoveredthat, when exposed to certain molds or dust mite proteins, brush cells inmices noses churn out inflammation-producing lipids, called cysteinylleukotrienes. The cells also made the lipids when encountering ATP, a chemical usedby cells for energy that also signals when nearby cells are damaged, as in aninfection. Mice exposed to allergens or ATP developed swelling of their nasaltissues. But mice that lacked brush cells suffered much less inflammation.

Such inflammation may lead to allergiesin some cases. The researchers havent yet confirmed that brush cells in humannoses respond to allergens in the same way as these cells do in mice.

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Hairy cells in the nose called brush cells may be involved in causing allergies - Science News

Immunology

New breakthrough discovery in immune system could treat all types of cancer – News Heads

New Delhi : A newly-discovered part of our immune system can be used to save and cure you from all types of cancers, say scientists.

A team of Cardiff University scientists discovered have discovered a method to kill prostate, breast, lung and other cancers in lab tests.

The findings from their study have been published in Nature Immunology. However, the procedure is yet to be tested on a patient, the scientists are positive and have a strong belief that this will turn in their favour.

Progress till date

Human body has its natural defence to the diseases, commonly known as immune system. The scientists were looking for "unconventional" and previously undiscovered ways the immune system naturally attacks tumours.

During the research, they found that T-cell inside human blood that keeps a check on the body to locate which part of the body has a threat to the disease and needs to be eliminated.

The difference is this one could attack a wide range of cancers.

"There's a chance here to treat every patient," researcher Prof Andrew Sewell told the BBC.

He added: "Previously nobody believed this could be possible.

"It raises the prospect of a 'one-size-fits-all' cancer treatment, a single type of T-cell that could be capable of destroying many different types of cancers across the population."

How does T-Cell work?

T-cells have "receptors" on their surface that allow them to "see" at a chemical level.

The Cardiff team discovered a T-cell and its receptor that could find and kill a wide range of cancerous cells in the lab including lung, skin, blood, colon, breast, bone, prostate, ovarian, kidney and cervical cancer cells.

Crucially, it left normal tissues untouched.

How would the treatment be done?

According to the scientists, a blood sample would be taken from the patient to locate T Cells then they will be genetically modified and placed back in the blood and then into the human body.

The new modified T cells will no locate the cancer-causing threats and would eliminate them automatically without causing any damage to other parts of our body.

Expert Researchers Reaction to the study

Lucia Mori and Gennaro De Libero, from the University of Basel in Switzerland, said the research had "great potential" but was at too early a stage to say it would work in all cancers.

"We are very excited about the immunological functions of this new T-cell population and the potential use of their TCRs in tumour cell therapy," they said.

Daniel Davis, a professor of immunology at the University of Manchester, said: "At the moment, this is very basic research and not close to actual medicines for patients.

"There is no question that it's a very exciting discovery, both for advancing our basic knowledge about the immune system and for the possibility of future new medicines."

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New breakthrough discovery in immune system could treat all types of cancer - News Heads

Immunology

Mundipharma Enters Partnership With Samsung Bioepis to Expand Biosimilars Into Hong Kong and Taiwan – Yahoo Finance

Mundipharma today announced a partnership with Samsung Bioepis to commercialize Samsung Bioepis first-wave biosimilar candidates in Taiwan and Hong Kong.

The partnership covers Samsung Bioepis biosimilar candidates in the field of immunology and oncology, including SB5 (adalimumab), SB4 (etanercept), SB3 (trastuzumab), and SB8 (bevacizumab).

Through the partnership, Mundipharma will be the exclusive commercialization partner, while Samsung Bioepis will remain the Marketing Authorisation Holder (MAH), responsible for clinical development, regulatory registration, and manufacture of the biosimilars.

"This partnership brings together Samsung Bioepis proven biosimilar development platform with Mundipharmas commercial acumen and market insight and ability to increase patient access to proven treatments," said Mundipharma CEO, Raman Singh. "This partnership will help to address the patient need in two important territories in Asia for immunology and oncology treatments," he added.

About Mundipharma

Mundipharmas independent associated companies are privately owned entities covering the worlds pharmaceutical markets. Mundipharma is a prime example of a company that consistently delivers high quality products while standing by the values that represent the company. Our mission is to alleviate the suffering of patients with cancer and non-cancer pain and to substantially improve their quality of life. Mundipharma is dedicated to bringing to patients with severe and debilitating diseases the benefit of novel treatment options in fields such as pain, oncology, oncology supportive care, ophthalmology, respiratory disease and consumer healthcare. For more information please visit: http://www.mundipharma.com.sg.

About Samsung Bioepis Co., Ltd.

Established in 2012, Samsung Bioepis is a biopharmaceutical company committed to realizing healthcare that is accessible to everyone. Through innovations in product development and a firm commitment to quality, Samsung Bioepis aims to become the world's leading biopharmaceutical company. Samsung Bioepis continues to advance a broad pipeline of biosimilar candidates that cover a spectrum of therapeutic areas, including immunology, oncology, ophthalmology and hematology. Samsung Bioepis is a joint venture between Samsung BioLogics and Biogen. For more information, please visit: http://www.samsungbioepis.com and follow us on social media Twitter, LinkedIn.

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Contacts

Stephenie VaskoChief Communications Officer & Head, Digital Strategy Asia Pacific, Latin America the Middle East & Africa+65-6303-9732 | media@mundipharma.com.sg

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Mundipharma Enters Partnership With Samsung Bioepis to Expand Biosimilars Into Hong Kong and Taiwan - Yahoo Finance

Immunology

@UMmedschool expert available to comment on coronavirus outbreak; he is studying the virus and how it spreads. – Newswise

MEDIA CONTACT

Available for logged-in reporters only

Newswise Matthew Frieman, PhD, Associate Professor of Microbiology and Immunology at the University of Maryland School of Medicine is available for interviews on the coronavirus outbreak in China that is spreading to other countries including the U.S. He plans to study the virus by synthesizing it in his lab and from samples provided to him from the Centers for Disease Control and Prevention.

His research goal is to create therapeutic interventions for viruses of public health concern by developing a detailed understanding of how the viruses interact with the host. His research has focused on the recently emerged and highly pathogenic coronaviruses: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Both viruses cause severe lung disease, are highly lethal and yet there are no FDA approved therapeutics that target them.

His work has been highlighted in The Washington Post, NPR, and STAT.

Quote: With new cases in Japan, Thailand, and now the U.S., and with the number of cases in China now totaling in the hundreds, there is clear evidence human-to-human spread of this virus, which will make it problematic to control.

Some of Dr. Friemans published research findings on these viruses and potential new treatments appear below:

Coleman CM, Sisk JM, Mingo RM,Nelson EA, White JM,Frieman MB. 2016.Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute RespiratorySyndromeCoronavirus and Middle East Respiratory Syndrome Coronavirus Fusion. JVirol 90:8924-8933.

Luke T, Wu H, Zhao J, Channappanavar R, Coleman CM, Jiao JA, Matsushita H, Liu Y, Postnikova EN, Ork BL, Glenn G, Flyer D, Defang G, Raviprakash K, Kochel T,Wang J, Nie W, Smith G, Hensley LE, Olinger GG, Kuhn JH, Holbrook MR, Johnson RF, Perlman S, Sullivan E,Frieman MB. 2016. Human polyclonal immunoglobulinfrom transchromosomic bovines inhibits MERS-CoV in vivo. Sci Transl Med 8:326ra321.

Dyall J, Coleman CM, Hart BJ,Venkataraman T, Holbrook MR, Kindrachuk J, Johnson RF, Olinger GG, Jr.,Jahrling PB, Laidlaw M, Johansen LM, Lear-Rooney CM,Glass PJ, Hensley LE,Frieman MB. 2014. Repurposing ofclinically developed drugs for treatment of Middle East respiratory syndromecoronavirus infection. AntimicrobAgents Chemother 58:4885-4893.

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@UMmedschool expert available to comment on coronavirus outbreak; he is studying the virus and how it spreads. - Newswise

Immunology

Scientists find immune cells that fight tumours from within – The Straits Times

TOKYO Lurking deep inside some tumours are "factories" full of immune cells that help the body fight a rearguard action against cancer and are key to helping some patients recover, new research has shown.

In recent years, doctors have turned to a new treatment for cancer - immunotherapy - that works by leveraging the body's immune system to fight tumours.

The technique has largely focused on white blood cells called T-cells, which are "trained" to recognise and attack cancer cells.

But the innovative treatment works well for only around 20 per cent of patients, so researchers have been trying to understand why some people respond better than others.

Three papers published last Thursday in the journal Nature point the way, identifying a key formation inside some tumours: tertiary lymphoid structures (TLS).

TLS function like factories or schools for immune cells that help the body fight cancer, said Professor Wolf Fridman, a professor emeritus of immunology at the Cordeliers Research Centre of the Paris Descartes University medical school, who led one of the studies.

He said the cells need to be educated in "schools" - the TLS - where they learn to recognise and attack cancer cells.

Key to the findings is that T-cells are far from the only immune cells capable of taking the fight to cancer. Researchers found the TLS were full of B-cells, a kind of immune cell that produces antibodies.

"We have been T-cell addicts for 15 years in cancer," Prof Fridman said. "We analysed these sarcomas to see what groups they had and what's striking is that these B-cells appeared."

Dr Beth Helmink, a fellow in surgical oncology at the University of Texas' MD Anderson Cancer Centre, who worked on a second study, said the research had changed perceptions of the role of B-cells in immunotherapy.

"Through these studies, we find that B-cells are not just innocent bystanders, but are themselves contributing in a meaningful way to the anti-tumour immune response," she said in a statement from the centre.

The discovery is a surprise, as an abundance of B-cells in cancer patients has sometimes been seen as a marker for poor prognosis.

But the studies found patients with high levels of B-cells inside TLS in their tumours were more likely to respond well to immunotherapy.

Dr Louisa James, a lecturer in immunology at Barts and the London School of Medicine and Dentistry, Queen Mary University of London, said: "This series of studies is exciting because (it represents) real progress in the treatment of different types of cancer."

Dr James, who was not involved in the studies, added: "In the short term, these results provide a new tool to help predict which patients are likely to benefit from treatment with immunotherapy and may also pave the way for improved treatments in the future."

There are still many unanswered questions, including why TLS form in some tumours and not others.

While it now seems clear that B-cells inside the structures play a key role in the success of immunotherapy, scientists are not sure precisely how.

It may be that the B-cells are on the front lines, producing antibodies that attack cancer cells efficiently - or they may be bolstering T-cells, or perhaps even doing both.

And not all TLS are created equal: The researchers found three categories, but only one type was "mature" enough to churn out cancer-fighting immune cells.

The research opens up promising new avenues, the authors said.

Initially, the findings could help doctors screen patients to see which of them are most likely to respond well to immunotherapy.

It could eventually mean more patients are successfully treated with the technique, said Professor Goran Jonsson, a professor of oncology and pathology at Lund University in Sweden, who worked on a third study.

"If we come up with a treatment that could enhance TLS formation, we could combine this with current immunotherapy regimens," he said. "Most likely, this would lead to more patients responding to immunotherapy."

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Scientists find immune cells that fight tumours from within - The Straits Times

Immunology

The babies ‘at risk of catching deadly illnesses’ in West Sussex – Spirit FM

The British Society for Immunology has urged the new government to deliver on its promise to develop the UKs first vaccine strategy to protect communities against nasty diseases.

Young children should get the so-called six-in-one jab, which protects against six serious infections including polio, whooping cough and diphtheria, in the first few months of their lives.

Public Health England data shows that 231 children in West Sussex who had their first birthday in the six months to September missed out on the vaccination.

But 94.8% of one year olds did have it, meaning the area was only just short of the 95% rate recommended by the World Health Organisation to prevent outbreaks.

The uptake rate for the South East over the period was 93.2%, while the figure across England stood at 92.1%.

Across England, the figure stood at 92.1%.

The British Society for Immunology said the uptake rate across England for the six-in-one vaccine among one year olds has averaged around 92% over the past year.

"Low levels of vaccination coverage matter as it means these diseases have the potential to spread within our communities, infecting unvaccinated people, with young babies and people with compromised immune systems particularly at risk.

"We urge the new government to deliver on its promise to develop the UKs first vaccine strategy and to fully fund immunisation services to ensure our communities are protected against these preventable diseases."

Dr Doug Brown, chief executive, The British Society for Immunology

But he also urged parents to make sure their children get the jabs.

"If you are worried your child hasnt received all the doses of the six-in-one vaccine, do make an appointment at your GP surgery.

"Its much better to get your child vaccinated than risk them catching one of these nasty diseases."

Babies should have three rounds of the six-in-one vaccination at eight, 12 and 16 weeks of age.

It helps them develop a strong immunity to diphtheria, hepatitis B, haemophilus influenza type b, polio, tetanus and whopping cough all described by the NHS as serious childhood diseases.

"Every child must be vaccinated against dangerous and potentially fatal diseases.

"Vaccine uptake is very high, at around 90%, for most childhood vaccines, but we are determined to drive rates up even further.

"Our new vaccination strategy, published in the new year, will consider a range of approaches to improve uptake."

Health minister, Nicola Blackwood

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The babies 'at risk of catching deadly illnesses' in West Sussex - Spirit FM

Immunology

Emerging Biologic Treatments for Allergies and Asthma – Pulmonology Advisor

A great deal of research into allergic diseases has yielded many new observations that have immediate implications for treatment.1-3 Epidemiologic studies in several countries have indicated that the prevalence of allergies and asthma has been steadily increasing during the past 2 decades.2 At the same time, recent investigations have identified multiple pathogenic entities and several distinct allergic diseases with specific phenotypic characteristics and treatment response profiles, including allergic rhinitis, atopic dermatitis (AD), angioedema, and asthma.2

These findings have all contributed to a game-changing evolution in the treatment of allergic disease that is rapidly moving forward. In 2018, Dagmar Simon, MD, from Bern University Hospital, Switzerland, observed in the first of 2 annual reviews, With the development of novel therapies, of which some have already been approved, we face a new era of disease management and, with that, probably a modification of the expected course of diseases. 2

Targeting Immune Mechanisms for Therapy

Many large-scale studies have expanded the understanding of the important role of the immune system in homeostasis and host defense, which has led to the exploration of small molecule and biologic therapies that target immune mechanisms in allergic diseases. 1-3 The pathogenesis of allergies is determined by a complex of overlapping mechanisms that produce different patterns of inflammatory symptoms, as immune cells distributed throughout the body respond to individual and environmental triggers, mediated by lipids, growth factors, chemokines, cytokines, and endothelial barriers.

This multifaceted etiology of allergic diseases, including asthma, makes it difficult to identify a single target for therapy, so novel biological agents are designed to influence particular segments of the pathogenic pathways. Several types of immunologic therapies, including IgE and interleukin-4 (IL-4), IL-13, and IL-5 therapies that target eosinophils and alarmins, have already been approved, based on efficacy in clinical trials against specific subtypes of allergies.

Omalizumab is a monoclonal antibody with a high binding affinity for IgE that has demonstrated good efficacy against asthma and allergic conditions such as AD, reducing the frequency, severity, and chronicity of symptoms by inhibiting the T2 inflammatory action of IgE.3 Omalizumab is considered an appropriate add-on therapy for patients with uncontrolled allergic asthma, as well as those with chronic urticaria.

The IL-4 and IL-13 pathways have been implicated in the production of inflammatory eosinophils in allergic diseases; IL-4 cytokines contribute to IgE mechanisms and hepatic proliferation, whereas IL-13 has effects that are limited mostly to barrier dysfunction and biological disturbances of the skin.3 Dupilumab is a monoclonal antibody that works as a dual inhibitor of IL-4 and IL-13 signaling. It has been approved for the add-on treatment of uncontrolled eosinophilic asthma, AD, and chronic rhinosinusitis with nasal polyps.

Expression of eosinophils has a particularly strong association to asthma by contributing to inflammatory obstruction.4 The protein granules in eosinophils can also cause irritation to the airway structure and trigger bronchial spasm.4 Cytokines such as IL-5 produced by eosinophils may also stimulate new eosinophil formation to promote an ongoing cycle of airway dysfunction.4

Monoclonal antibodies (mAbs) that target the IL-5 pathway, including mepolizumab, reslizumab, and benralizumab, have demonstrated rapid reduction of eosinophil levels in patients with severe, uncontrolled asthma.3,4 All 3 drugs have been shown to reduce asthma exacerbations by about 50%.4 The challenges to IL-5 mAbs are that only about 50% of patients with severe asthma respond to these therapies, and the improvement in exacerbations may not be accompanied by improved lung function and quality of life.3 In addition, the benefits to IL-5 mAbs are lost with discontinuation of therapy, which may even produce rebound eosinophilia.3

Key mediators of homeostasis are cytokines such as thymic stromal lymphopoietin and IL-25 and IL-33, known as alarmins, as they initiate inflammation in response to damage or insult to the body. Tezepelumab is undergoing clinical trials as a first-in-class human mAb designed to block thymic stromal lymphopoietin, whereas antibodies to IL-33 and IL-25 are in the early stages of development. 3

Next Steps for Biologic Therapies

A multitude of dynamic internal and environmental factors have a continuing effect on the status of the immune system, eliminating the possibility of a single therapeutic target for many patients with resistant types of allergic diseases, particularly asthma. And although several biologic therapies have shown great promise, researchers are as-yet unable to identify the patients who are most likely to respond to these interventions. A 2020 review by Agache et al3 reported that achieving selective immune modulation without altering the healthy immune response and with a long-lasting disease modifying effect is still not reached. The immediate goals in biologic therapies for allergies and asthma are to develop biomarkers to identify patients who are most likely to respond to these therapies and to monitor disease severity. As experience with biological therapies continues to grow, they are expected move from their current position as add-on therapies for severe allergic disease to play a more prominent role in treatment strategies for many more allergy patients.

References

1. Simon D. Recent advances in clinical allergy and immunology 2019. Int Arch Allergy Immunol. 2019;180:291-305.

2. Simon D. Recent advances in clinical allergy and immunology. Int Arch Allergy Immunol. 2018;177:324-333.

3. Agache IO, Catalina C, Laculiceanu A, Rogozea L. Critical points on the use of biologicals in allergic diseases and asthma. Allergy Asthma Immunol Res. 2020;12:24-41.

4. Busse W. Biologic treatments for severe asthma: a major advance in asthma care. Allergol Int. 2019;68:158-166.

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Emerging Biologic Treatments for Allergies and Asthma - Pulmonology Advisor

Immunology

The Week Ahead: Abbott Laboratories and Johnson & Johnson Due – Morningstar.com

Earnings season continues next week with a medley of narrow- and wide-moat companies announcing earnings.

Johnson & Johnson (JNJ) and Abbott Laboratories (ABT) will both release earnings on Wednesday.

Johnson & Johnson has had steady growth for the past several years, and we expect this trend to continue with its fourth-quarter earnings. The company is expected to beat fourth-quarter earning estimates despite a recent onslaught of lawsuits. It is currently fighting over 16,000 asbestos-related lawsuits connected to its talcum powder products. Last October, Johnson & Johnson was also ordered to pay out $8 billion in a Risperdal (an anti-psychotic drug) product liability case.

Our director of equity analysis for North America, Damien Conover, stated that while we expect the quarters results to be under some pressure from patent losses in the firms oncology and immunology divisions, we expect the full-year 2019 earnings growth to be close to 6%. While patent pressures will likely continue into 2020, Johnson & Johnsons diversified platform should enable the firm to offset generic competition. Expected updates on the firms robotic device platforms should also help reinvigorate growth in the companys device segment. However, overall, from a valuation perspective, we view the company as slightly overvalued with some concerns on the firms late-stage pipeline weighing on our fair value estimate.

Abbott Laboratories is changing up its leadership this year with its senior vice president of finance and controller, Robert Funck Jr., becoming CFO and its president and operating chief, Robert Ford, becoming CEO this March. Miles White, the companys current CEO since 1999, will stay on as the executive chairman. Abbott Laboratories is currently waiting upon FDA approval for its new glucose monitor, Freestyle Libre 2.

Overall, the healthcare sector has increased 22% as of the end of 2019, which, while solid performance, underperformed the broader equity market performance of 31%. Concerns around potential healthcare policy change in the United States have increased uncertainty in the sector and have affected performance.According to Conover, although U.S. policy reform is probable, it is unlikely that a major overhaul will occur that will affect drug pricing power, which is expected to remain steady. Additionally, while the sector is slightly overvalued, with the most overvalued stocks in the device and diagnostics industries, there are some pockets of undervalued stocks in the drug and biotech industries.

On Tuesday, IBM (IBM), Netflix (NFLX), Capital One Financial (COF), UBS (UBS), Progressive (PGR), and TD Ameritrade (AMTD) will all be reporting earnings.

Thursday brings another round of earnings announcements, with Microsoft (MSFT), Procter & Gamble (PG), Intel (INTC), Comcast (CMCSA), and Discover Financial (DFS) reporting.

Microsoft has done well in recent months, earning a coveted $10 billion contract with the Joint Enterprise Defense Infrastructure Contract in October. The company has been focusing on the proliferation of its Azure platform and customer adoption of hybrid cloud environments on said platform.

In other economic news, Wednesday also brings with it the FHFA Housing Price Index for January, the Existing Home Sales report for December, and the EIA Crude Oil Inventories for Jan. 18.

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The Week Ahead: Abbott Laboratories and Johnson & Johnson Due - Morningstar.com

Immunology

Chemosensory Cells in the Nose Play a Role in Allergic Reactions – The Scientist

There are a lot of unknowns when it comes to understanding how the mammalian respiratory tract responds to allergens, but a study published today (January 17) in Science Immunology, offers new insight. Researchers identified a group of epithelial cells in the mouse nose that are capable of responding to allergens directly and also to ATP released in response to allergens. When exposed to allergens, these so-called brush cells secrete cysteinyl leukotrienes, proinflammatory lipids that have been previously shown to come mostly from immune cells and have been linked to asthma and allergies.

We have been interested in how allergens are recognized by the airway epithelium and how they drive immune responses that are biased towards allergic inflammation, says coauthor Lora Bankova of Harvard Medical School.

Previous research had shown that tuft cells, a solitary chemosensory cell type found in the intestine, are responsible for orchestrating immunity to parasitic worms in the gut, which trigger the same type of immune response as allergens. To determine whether there might be cells playing the same role in the airway epithelium, she and her colleagues investigated a similar cell type in the mouse trachea: brush cells. In work published in 2018, they analyzed the gene expression profile of brush cells and found that brush cell activation was important for airway inflammation.

In the trachea, brush cells are only about half of a percent of the total number of cells. These small numbers made it hard to do in vitro or ex vivo cultures in which it would be possible to directly stimulate them and see what happens, Bankova explains. So the research team looked for these cells elsewhere in the airway. In the current study they found that there are solitary chemosensory cells with similar transcriptional profiles to the tracheal brush cells present in much larger numbers in the mouse nose, where they contribute 48 percent of the total cells.

Because theyre so abundant we were actually able to isolate them and study them directly to see what activates them, what can they produce in response to stimulation, Bankova tells The Scientist.The researchers isolated nasal brush cells from mice and incubated them with ATP, which functions as a cellular stress or damage signal, or with allergens from dust mites or mold.

In response, the brush cells released proinflammatory cysteinyl leukotrienes at amounts comparable to or exceeding what immune cells produced when the research team stimulated them. Brush cell production of these lipids, and the lower levels generated by other cell types, indicate that the epithelial cells are likely the dominant source of cysteinyl leukotrienes in the nose. The researchers also showed that mice without brush cells had a reduced amount of allergic inflammation in response to an allergen.

Allergen activates them, and theyre important for generating the cysteinyl leukotrienes and allergic inflammation in that setting, says Bankova. She explains that its likely that theyre also responding to other sorts of damage in the airway epithelium because they release cysteinyl leukotrienes in response to ATP as well.

That ATP serves as a ligand for brush cells is the most surprising finding, says Christoph Schneider, a biologist at the University of Zurich who did not participate in the study. He adds that open questions include whether or not brush cells are the sole target of ATP and sole source of cysteinyl leukotrienes and whether this is true only for these airway brush cells or whether the same ATP effect is also observed in other situations, in other organs, et cetera.

To develop an asthma-like syndromeespecially if its allergic in natureyou have to have sensitization and then a subsequent response to challenge, so this is providing a mechanism by which the epithelium by itself is critical for sensitization, says Teal Hallstrand, a pulmonary physician at the University of Washington who was not involved in the work. Id be very excited to learn about whether or not people with asthma have an alteration in the number of these cells in their airways and what specific physiological effect that has.

S. Ualiyeva et al., Airway brush cells generate cysteinyl leukotrienes through the ATP sensor P2Y2, Science Immunology, doi:10.1126/sciimmunol.aax7224, 2020.

Abby Olena is a freelance journalist based in Alabama. Find her on Twitter@abbyolena.

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Chemosensory Cells in the Nose Play a Role in Allergic Reactions - The Scientist