The quest for new therapeutics and better follow-up of patients with inflammatory bowel diseases (IBD) requires the clearest possible picture of the immunological mechanisms underlying these complex pathologies. We identified recently a potential new player in this destructive game, a non-conventional T cell subset called Mucosal-Associated Invariant T (MAIT) cells. These cells were initially identified on the basis of their use of a semi-invariant TCR, made of the invariant Vα7. 2–Jα33 TCRα chain (now TCRAV1S2–AJ33) paired to a limited number of different TCRβ chains (1). Human MAIT cells are mostly CD8+ T cells with an effector/memory phenotype and expression of various chemokine receptors involved in extra-lymphoid migration. They also express most markers associated with IL-17 producing T cells, such as RORγt, high CD161, IL-23R, and CD26. They make up to 10% of peripheral blood and intestinal lamina propria T cells, and are even more abundant in the liver (2). The most striking feature of MAIT cells is their recognition of highly conserved microbial-derived metabolites associated to a monomorphic MHC class-I like molecule, MR1 (MHC-related 1)(3). These ligands structurally belong to the pterin family and are derived from the riboflavin synthesis pathway. Recent experiments showed that virtually all MAIT cells are stained by fluorescent MR1 tetramers loaded with these specific metabolites. This pathway is absent in vertebrates, but many bacterial and fungal species produce riboflavin and therefore, MAIT cells-specific ligands. In this respect, these metabolites behave like microbial innate signals, and may alert MAIT cells that an invasive infection is on-going. Upon activation, MAIT cells release TNFα, IFNγ and become cytotoxic; they also produce IL-17 in specific conditions. In fact, they represent the great majority of naturally occurring IL-17-producing CD8+ T cells in the human peripheral blood. These cells are very likely to perform important anti-microbial functions, as suggested in humans and mice models (4). However, numerous reports suggest that MAIT cells are recruited from the blood to inflamed tissues in chronic inflammatory diseases such as multiple sclerosis, psoriasis, and systemic lupus, among others. We recently showed that Crohn’s disease (CD) patients display a decreased number of blood MAIT, balanced by their accumulation in the inflamed portions of the gut (5). As already stated, MAIT cells are equipped with chemokine receptors allowing migration toward tissues, in particular in conditions of inflammation. Therefore, it might be suggested that they are non-specifically attracted to sites of inflammation and are only bystanders in this process. However, we wish to discuss in this opinion article the arguments in favor of a relevant role for this T cell subset, at least in the context of CD.

We showed in our study that blood MAIT cells from CD patients showed an altered phenotype, increased in vivo proliferation, and, interestingly, a shift in cytokine production with decreased IFNγ and increased IL-17 production (5). While this description does not allow any formal conclusions about the direct involvement of MAIT cells in the pathophysiology of the disease, it has several important implications. Indeed, although blood MAIT cells may be non-specifically attracted to the inflamed gut by locally produced chemokines, it must be reminded that a significant number of them are found in the gut lamina propria in the healthy intestine. Therefore, it is more than likely that these intestinal cells are also activated in CD, and produce cytokines, which are highly relevant to the pathology, ie, IFNγ, TNFα, and IL-17. Hence, it is difficult to …