Reduced circulating MAIT cells in obesity

Abstract

Abstract Obesity is a major risk factor for certain types of cancer and the mechanisms by which obesity contributes to tumor metastasis are not well understood. Whereas the immune system is essential for fighting against tumors, in the context of obesity, systemic chronic inflammation with altered immune responses are found. Recent studies have revealed that the gut microbiota also contributes to obesity and the pathology associated with that disease. Mucosal-associated innate T (MAIT) cells are a unique subpopulation of T cells that are characterized by the expression of a semi-invariant TCR a chain (Vα19 in mice; Vα7.2 in humans). Although the development and maturation of MAIT cells require the gut microbiota and antigen presenting molecule MR1, the actual function of MAIT cells has not been well studied. We have found reduced circulating MAIT cells in obese patients as compared to age- and gender-matched healthy donors. Using real-time PCR to determine the expression levels of the invariant TCR of MAIT cells and classical T cell transcription factors, we found that, although no difference was observed in any gene expression analyzed between samples from obese patients or healthy donors, mRNA expression of the Vα7.2 TCR positively correlated with the transcription factor TBX21 (found in T helper 1 cells) and BCL6 (found in follicular helper T cells). Our work suggests that obesity alters the number of MAIT cells. The correlation of MAIT cell TCR gene expression with transcription factors of classical effector T cells, suggests there may be transcriptional pathways linking MAIT cells to the function of conventional T cells. Future work will focus on determining how obesity impacts the function of MAIT cells.