Obesity increases the production of proinflammatory mediators from adipose tissue T cells and compromises TCR repertoire diversity: Implications for systemic inflammation and insulin resistance
Emerging evidence suggests that increases in activated T cell populations in adipose tissue may contribute toward obesity-associated metabolic syndrome. The present study investigates three unanswered questions: 1) Do adipose-resident T cells (ARTs) from lean and obese mice have altered cytokine production in response to TCR ligation?; 2) Do the extralymphoid ARTs possess a unique TCR repertoire compared with lymphoid-resident T cells and whether obesity alters the TCR diversity in specific adipose depots?; and 3) Does short-term elimination of T cells in epididymal fat pad without disturbing the systemic T cell homeostasis regulate inflammation and insulin-action during obesity? We found that obesity reduced the frequency of naive ART cells in s.c. fat and increased the effector-memory populations in visceral fat. The ARTs from diet-induced obese (DIO) mice had a higher frequency of IFN- γ+, granzyme B+ cells, and upon TCR ligation, the ARTs from DIO mice produced increased levels of proinflammatory mediators. Importantly, compared with splenic T cells, ARTs exhibited markedly restricted TCR diversity, which was further compromised by obesity. Acute depletion of T cells from epididymal fat pads improved insulin action in young DIO mice but did not reverse obesity-associated feed forward cascade of chronic systemic inflammation and insulin resistance in middle-aged DIO mice. Collectively, these data establish that ARTs have a restricted TCR-Vβ repertoire, and T cells contribute toward the complex proinflammatory microenvironment of adipose tissue in obesity. Development of future long-term T cell depletion protocols specific to visceral fat may represent an additional strategy to manage obesity-associated comorbidities. Copyright © 2010 by The American Association of Immunologists, Inc.
Publication Source (Journal or Book title)
Journal of Immunology
Yang, H., Youm, Y., Vandanmagsar, B., Ravussin, A., Gimble, J., Greenway, F., Stephens, J., Mynatt, R., & Dixit, V. (2010). Obesity increases the production of proinflammatory mediators from adipose tissue T cells and compromises TCR repertoire diversity: Implications for systemic inflammation and insulin resistance. Journal of Immunology, 185 (3), 1836-1845. https://doi.org/10.4049/jimmunol.1000021