Accumulating data suggest that the relationship between obesity and inflammation is a two-way street. Obesity can alter the types of immune responses seen in inflammatory diseases, while the immune system may regulate metabolism and features of adiposity. Understanding this complex interplay between metabolic state, immunity, and inflammation could lead to insights on how to best modulate the immune response in inflammatory diseases, such as atopic dermatitis, rheumatoid arthritis, and osteoarthritis.
“As immunologists, we have spent decades understanding the factors and pathways involved in T-cell differentiation and function,” said Sagar Bapat, MD, PhD, Assistant Professor, University of California, San Francisco. “This has led to several targeted biologic therapies for various autoimmune and inflammatory diseases. But most of this work was done under normal metabolic conditions. We don’t have a good understanding of how metabolic state affects T-cell function and can subsequently impact disease and treatment.”
Dr. Bapat will present his research on the impact of metabolic state on T cells and inflammation during Tipping the Scale: Interactions Between Obesity and Inflammation on Tuesday, Nov. 14, from 2–3 p.m. PT in Room 31A-C of the San Diego Convention Center. The session will be available on demand within 24 hours for registered ACR Convergence 2023 participants.
In a mouse model of atopic dermatitis, Dr. Bapat’s group found that obesity not only increases disease severity but also changes the immune response, which ultimately affects the efficacy of anti-inflammatory treatments.
“Metabolic state matters,” Dr. Bapat said. “Our work shows that obesity can functionally change the inflammatory state of a disease. This can have consequences on both disease severity as well as treatment efficacy. We’ve seen that treatments that work in a lean mouse can actually make disease worse in an obese mouse because they don’t target the right inflammatory response.”
Dr. Bapat will discuss the mechanisms by which obesity modulates T-cell function and his work on identifying targetable factors to restore a more normal inflammatory response under conditions of obesity. He said that, while their work started in atopic dermatitis, many of the mechanisms and factors involved appear to be generalizable across different inflammatory diseases.
While Dr. Bapat will focus on the impact of obesity on immune responses, Taku Kambayashi, MD, PhD, Professor of Pathology and Laboratory Medicine, University of Pennsylvania, will discuss the inverse of this relationship — how immune cells can influence metabolism. His research has elucidated a new role for T cells in inducing weight loss, highlighting the involvement of the skin in metabolism.
His lab has shown that the type 2 cytokine thymic stromal lymphopoietin (TSLP) can increase regulatory T cell numbers and may be effective at preventing autoimmune and inflammatory conditions.
More recent work showed that TSLP can also induce weight loss in obese mice by promoting the secretion of lipids from the sebaceous glands in the skin via a T-cell-mediated mechanism.
“This role of T cells in skin barrier function and metabolism was highly unexpected,” Dr. Kambayashi said. “We’ve seen that certain types of inflammatory responses can induce sebaceous gland function, resulting in fairly severe weight loss by promoting metabolic changes at the skin.”
Dr. Kambayashi noted that the metabolic role of the skin is often overlooked.
“People tend to focus on the liver and adipose tissue when they think of metabolism,” he said. “It seemed far-fetched that we can induce such severe weight loss by secreting lipids. But the skin is the largest organ in the body and has a remarkable effect on regulating systemic metabolism.”
Given the number of rheumatologic diseases characterized by inflammation near the skin, Dr. Kambayashi stressed that it is worth considering that the weight loss that occurs in certain types of inflammatory diseases may be related to the metabolic nature of the skin.
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