Mucosal‐associated invariant T cells in autoimmune and immune‐mediated diseases

Abstract

Autoimmune and inflammatory diseases have complex etiologies not fully understood. Both innate and adaptive immune cells are involved in the pathogenesis of these diseases. Mucosal-associated invariant T (MAIT) cells express an invariant TCRα chain (Vα7.2-Jα33 in humans and Vα19-Jα33 in mice) and recognize the conserved MHC-I-related molecule MR1 presenting bacterial metabolites derived from the synthesis of vitamin B. MAIT cells harbor tissue homing properties and produce inflammatory cytokines, suggesting that MAIT cells may play a key role in autoimmune and inflammatory diseases. In this review, we described the current knowledge on MAIT cells in these pathologies, based on patients analyses as well as mouse models. While most of the studies support a deleterious role of MAIT cells in tissue inflammation and destruction, a few reports suggest a protective role of MAIT cells. MAIT cells could represent a new biomarker of disease progression, and a better knowledge of their function might open new avenues for therapeutic strategies based on their manipulation.

Development of mucosal‐associated invariant T cells

“…For instance, MAIT cells isolated from the female genital tract express more IL‐17 in response to microbial stimuli compared to MAIT cells from peripheral blood . Moreover, tissue resident MAIT cells isolated from human liver vascular beds were the dominant population of IL‐17 producing T cells from this tissue and several studies have reported a role for IL‐17 producing MAIT cells in various autoimmune diseases (reviewed in this issue by Rouxel and Lehuen) . Accordingly, mice and humans contain functionally distinct populations of MAIT cells, although the precise molecular mechanisms that underpin the differentiation into each distinct population remain largely unknown.…”

MAIT cells: the end of the beginning?

“…5 Given their potential for stimulation via "danger" signals, MAIT cells may also be involved more broadly in host defense and inflammation. This aspect is explored in reviews on auto-immune disease 6 and antiviral responses. 7 The emerging picture from these reviews and the original data they describe is of a fascinating cell type, with important protective and also pathological potential.…”

“…Given their potential for stimulation via “danger” signals, MAIT cells may also be involved more broadly in host defense and inflammation. This aspect is explored in reviews on auto‐immune disease and antiviral responses …”

Characterization and Purification of Mouse Mucosal‐Associated Invariant T (MAIT) Cells

“…MAIT cells are present in most mammals and reside in mucosal and other tissues as well as in the circulation (Boudinot et al., ; Treiner et al., ). In humans, these cells are relatively abundant (accounting for 5% of T cells in blood on average; Ben Youssef et al., ; Gherardin et al., ; Koay et al., ; Rahimpour et al., ), and their numbers have been reported to change in several disease states and infections (Chiba, Murayama, & Miyake, ; Cosgrove et al., ; Rouxel & Lehuen, ). Methods for analysis of MAIT cells in human samples and further information on MAIT cells are provided in a parallel unit (see Current Protocols article; Souter et al., ).…”