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How obesity can rewire the immune system and the response to immunotherapy—and how to change that

NOMIS Awardee Ronald Evans, NOMIS researcher Ye Zheng and their colleagues have discovered why immune treatments for allergies and asthma might not be as effective in obese mice and humans. Their findings were published in Nature.

LA JOLLA—When mice with atopic dermatitis—a common type of allergic skin inflammation—are treated with drugs that target the immune system, their thickened, itchy skin generally heals quickly. But scientists have now discovered that the same treatment in obese mice makes their skin worse, instead. That is because obesity changes the molecular underpinnings of allergic inflammation, both in mice and humans.

For the new study, researchers at the Salk Institute, Gladstone Institutes and UC San Francisco (UCSF) teamed up. Their findings, reported in the journal Nature on March 30, 2022, shed light on how obesity can change the immune system and, potentially, how clinicians might be able to better treat allergies and asthma in obese people.

Top from left: Ye Zheng, Michael Downes, Ronald Evans, Annette Akins and Yuqiong Liang (Photo: Salk Institute)
Bottom from left: Alex Marson and Sagar Bapat
(Photos, from left: Michael Short/Gladstone Institutes and Noah Berger)

“Our findings demonstrate how differences in our individual metabolic states can have a major impact on inflammation, and how available drugs might be able to improve health outcomes,” says Salk Professor Ronald Evans, co-senior author, director of Salk’s Gene Expression Laboratory, and the March of Dimes Chair in Molecular and Developmental Biology at Salk.

“We’re living in an era when the rate of obesity is increasing around the world,” says Professor Alex Marson, co-senior author and director of the Gladstone-UCSF Institute of Genomic Immunology. “Changes in diet and body composition can affect the immune system, so we have to think about how diseases that involve the immune system might differ between individuals.”

Different Types of T Cell Responses

recent study estimated that about half of the adults in the United States will be classified as obese by the year 2030. Researchers also know that obesity, sometimes classified as a chronic inflammatory state, alters the immune system in myriad ways. Clinicians have reported that people with obesity often seem to have different courses of disease—from infections and allergies to cancer—and respond differently to some treatments.

During his graduate studies at Salk and subsequent research in the Marson lab, first author Sagar Bapat—now a pathologist and faculty at UCSF—wanted to know, at a molecular level, how obesity affected atopic dermatitis. He discovered that when mice were made obese by eating a high-fat diet prior to the induction of dermatitis, they developed more severe disease than lean animals. To understand why, he and his colleagues analyzed the immune cells and molecules that were active in each group of mice.

“What we were expecting to see in the obese mice was just a greater degree of the same kind of inflammation,” says Bapat. “Instead, we saw a completely different kind of inflammation.”

The body’s helper T cells, which help protect against infection but also become overactive in autoimmune disease or allergies, can be grouped into three classes: TH1, TH2, and TH17 cells. Scientists had considered atopic dermatitis a TH2 disease; that means the TH2 cells are the ones causing the skin inflammation.

Continue reading this Salk Institute release

Read the Nature publication: Obesity alters pathology and treatment response in inflammatory disease


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NOMIS Researchers

Professor, director of Salk’s Gene Expression Laboratory and holder of the March of Dimes Chair in Molecular and Developmental Biology
Salk Institute for Biological Studies
Associate Professor - NOMIS Center for Immunobiology and Microbial Pathogenesis
Salk Institute for Biological Studies
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