Abstract
Microfold (M) cells are located in the epithelium covering mucosa-associated lymphoid tissues, such as the Peyer's patches (PPs) of the small intestine. M cells actively transport luminal antigens to the underlying lymphoid follicles to initiate an immune response. The molecular machinery of M-cell differentiation and function has been vigorously investigated over the last decade. Studies have shed light on the role of M cells in the mucosal immune system and have revealed that antigen uptake by M cells contributes to not only mucosal but also systemic immune responses. However, M-cell studies usually focus on infectious diseases; the contribution of M cells to autoimmune diseases has remained largely unexplored. Accumulating evidence suggests that dysbiosis of the intestinal microbiota is implicated in multiple systemic diseases, including autoimmune diseases. This implies that the uptake of microorganisms by M cells in PPs may play a role in the pathogenesis of autoimmune diseases. We provide an outline of the current understanding of M-cell biology and subsequently discuss the potential contribution of M cells and PPs to the induction of systemic autoimmunity, beyond the mucosal immune response.
Highlights
The mucosal surface forms a border between our body and the outer world
The mucosal surface is protected from invasion of foreign antigens by efficient and size-selective physical shields composed of mucin and glycocalyx layers and chemical barriers including antimicrobials and antigen-specific secretory immunoglobulin (Ig) A (S-IgA) [2]
Given that these segmented filamentous bacteria (SFB)-induced Th17 responses are mainly induced in Peyer’s patches (PPs) and isolated lymphoid follicles [109], PPs may be the primary site for the autoimmune response in insulitis development in nonobese diabetic (NOD) mice
Summary
The mucosal surface forms a border between our body and the outer world. The human intestinal mucosa is exposed to food-derived antigens, pathogens, and more than 40 trillion commensal bacteria [1]. Specialized epithelial microfold (M) cells located in the follicle-associated epithelium (FAE) are responsible for antigen uptake in GALTs and nasopharynx-associated lymphoid tissue and play a central role in immune surveillance on the mucosal surface [7] (Figure 1). A recent study demonstrated that M celldependent antigen uptake might facilitate mucosal and systemic immune responses, such as antigen-specific IgG production [9]. This suggests that antigen uptake by M cells might play a pathological role in the production of autoantibodies and the development of autoimmune diseases. We discuss recent advances in the molecular basis of differentiation and functions of M cells and the potential implication of GALT in the etiology of various autoimmune diseases
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