How does obesity alter the immune system, and even immunotherapy response?

In the new study, researchers from the Gladstone Institutes, the Salk Institute for Biological Studies and the University of California, San Francisco (UCSF) collaborated

Different types of T cell responses

A recent study estimated that by 2030, roughly half of American adults will be classified as obese

Sagar Bapat, MD (now a pathologist and faculty member at UCSF) on the study, Alex Ma, MD, senior author of the study and director of the Gladstone-UCSF Institute for Genomic Immunology Working in the lab of Alex Marson, he found that when mice became obese by eating a high-fat diet before inducing dermatitis, they developed more severe disease than lean animals

"What we expected to see in the obese mice was just more severe inflammation," Bapat said.

The body's helper T cells help protect against infection but can also become overactive in autoimmune diseases or allergies and can be divided into three categories: TH1, TH2 and TH17 cells

In lean mice with atopic dermatitis, Bapat and his colleagues did find that TH2 cells were active

In recent years, scientists have developed drugs to treat atopic dermatitis by inhibiting the response of TH2 cells

"The treatment becomes a powerful counter-treatment," Bapat said

The researchers suspect that dysfunction of a protein called PPAR-gamma may mediate the link between obesity and inflammation

When the scientists treated obese mice with atopic dermatitis with a PPAR-gamma-activating drug called rosiglitazone, the animals' skin improved and the disease's molecular structure shifted from TH17 inflammation to TH2 inflammation

"Basically, we immunized the mice to 'defat' the mice without changing their body weight," Bapat said

back to patient

The team also analyzed data from human allergic disease patients, including 59 patients with atopic dermatitis and hundreds of patients with asthma (another disease with a similar immune system response) who participated in a large Longitudinal study

While more research in humans is needed, data suggest that, in humans and mice, obesity induces a shift in inflammation that leads to pathological changes in allergic disease and the effectiveness of immunotherapies targeting TH2-related inflammation
.

"We now want to know more about how the T-cell switch occurs," said senior author Ye Zheng, Ph.
D.
, associate professor in the Salk NOMIS Center for Immunobiology and Microbial Pathogenesis
.
"There are more details yet to be discovered, and they may be associated with a range of allergy- and asthma-related diseases
.
"

However, the new study already points out that combining treatments targeting TH2 inflammation with PPAR-gamma drugs such as rosiglitazone could treat obese patients with atopic dermatitis
.

"In this case, our scientific findings can be applied very safely and rapidly to treatment in humans," Evans said.
"
Our preclinical findings suggest that these FDA-approved drugs may have unique combination treatments for some patients.
benefit
.
"

Obesity Alters Pathology and Treatment Response in Inflammatory Disease