Significance and Biological Importance of Mucosal Associated Invariant T Cells in Inflammatory Bowel Disease Patients

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic inflammatory diseases of unknown origin. IBD has become a global disease with increasing incidence in newly industrialized and westernized countries. Genetic and environmental factors with inadequate host immune response to gut flora appear to play important roles in the pathogenesis of IBD. Adaptive immune response has been classically considered to play a major role in IBD pathogenesis .

Infiltrating lymphocytes including T helper (Th) 1 cells and Th17 cells can lead to the development of intestinal lesions . However, recent evidences suggest that innate immune response is equally important in inducing gut inflammation . Altered epithelial barrier function and aberrant innate immune responses contribute to intestinal inflammation in IBD patients.

Mucosal-associated invariant T (MAIT) cells are innate lymphocytes that express a conserved invariant Tcell receptor (TCR) Vα7.2-Jα33 chain paired with a limited set of Vβ chains. Using distinct pairs of TCR chains, MAIT cells can recognize bacteria-derived riboflavin (vitamin B2) metabolites presented by MHC(major histocompatibility complex) class 1b-like related protein (MR1).

Upon MR1-dependent recognition of antigens, MAIT cells are activated to rapidly release Th1/Th17 proinflammatory cytokines (i.e., interferon [IFN]-γ, tumor necrosis factor [TNF]-α, and interleukin [IL]-17 and cytotoxic molecules (i.e.,granzyme and perforin) to kill infected host cells.

MAIT cells are abundant in peripheral blood where they where they express gut-homing chemokine receptors such as CCR6(chemokine receptor type 6) and CCR9(chemokine receptor type9). They are also abundant in intestinal mucosa where they likely confront normal flora or pathogenic bacteria producing bacterial ligands.