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Imitation is the best form of… treating IBD?
Hebbandi NR, Ronchi F, Wang J, et al. A gut microbial mimic that hijacks diabetogenic autoreactivity to suppress colitis. Cell 2017;171:655–67.
The commensal microbiota regulate T cell homeostasis. Therefore, variation in microbiota can affect autoimmunity. Many microbial antigens contain mimics of self-antigens, and this paper identifies Bacteroides integrase as one. It also suggests that this integrase recruits specific T cells and could have therapeutic potential in IBD. Type 1 diabetes in non-obese mice is due to CD4+ and CD8+ T cell-dependent reactions to pancreatic beta islet cells. CD8+ T cells recognise IGRP206–214 (islet-specific G6P-catalytic subunit - related protein). Its high-avidity clones promote disease by killing beta cells, but its low-avidity clones suppress disease by targeting pancreatic antigen-presenting cells. It was hypothesised that this subset of T cells may recognise another epitope. By searching for homologous amino acid sequences, it was discovered that the integrase encoded by Bacteroides species is a mimic of IGRP206–214 and is recognised by the same IGRP206–214 reactive CD8+ T cells. Surprisingly, Bacteroides integrase recruits diabetogenic CD8+ cells to the gut and suppresses chemical-induced dextran sulfate sodium (DSS) colitis in mice. It does so by targeting gut dendritic cells. This suppression is MHC class I dependent, as CD11 deletion in mice still afforded protection against colitis. Immunocompromised mice were monocolonised with Bacteroides, both integrase competent and integrase deficient, then exposed to DSS to induce colitis. Interestingly, human peripheral blood CD8+ T cells also recognise this gut microbial mimic. It is novel that a molecule generated by the microbiome can mimic an autoantigen. This molecular mimicry may contribute to maintenance of normal immune homeostasis and these specific T cells may have potential in IBD therapy.
Adaptive immune cell crosstalk promotes HCC formation in NAFLD
Shalapour S, Lin X, Bastian I, et al. Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity. Nature 2017;551:340–5.
Despite the advent of immune checkpoint inhibitors as effective anticancer therapies, …
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