Editors' ChoiceMicrobiome

What’s bugging your gut?

See allHide authors and affiliations

Science Translational Medicine  12 Aug 2015:
Vol. 7, Issue 300, pp. 300ec139
DOI: 10.1126/scitranslmed.aad0227

The gastrointestinal microbiome has been implicated in shaping host immune and metabolic responses. Regulatory T cells (Tregs) play a central role in this process. Although both commensal bacteria and pathogenic bacteria activate host pattern recognition receptors, such as Toll-like receptors, it is not clear how Tregs sensing commensals promote tolerance. To address this issue, Wang and colleagues employed a mouse model using Myd88-deficient Tregs (Foxp3EGRP-CreMyD88d/d) to elucidate the role of MyD88 in the induction of mucosal Tregs and the mechanisms to promote healthy commensalism. The authors assessed differences in Tregs and their effect on the regulation of microbiota and gut inflammation.

The authors discovered that MyD88 signaling promoted the generation of antigen-specific–induced Tregs at gut mucosa, and that Treg cell–specific MyD88 deficiency increased immune dysregulation and aggravated the severity of experimental colitis. Compared with mice with intact MyD88Tregs, these mice exhibited significantly decreased iTreg number and IL-10+Foxp3+ cells with an emergence of IL-17+ and RORγt+ cells in the gut. In colitis models, disease was more severe. This suggests that defects in MyD88 signaling–Tregs resulted in colonic inflammation via T helper 17 (TH17) skewing. The authors also showed that Treg cell–specific MyD88 deficiency altered gut microbial communities to those that promote TH17 inflammation, impaired intestinal IgA production, and allowed bacteria to translocate deeper into tissues. Restoration of IgA in these mice inhibited TH17 skewing and decreased bacterial penetration. This suggests that Tregs promote IgA production to control bacterial exposure and inhibit inflammation.

Together, these data suggest that Tregs promote tolerance and limit inflammation through MyD88 signaling. Treg exposure to symbiotic bacteria promoted IL-10+Induced-Treg number, promoted IgA production to influence commensal communities, and controlled inflammation in experimental colitis in a MyD88-dependent manner. These functions enable the maintenance of healthy commensalism and restrain microbiota-driven dysregulated immune responses. This work provides exciting insight into how Tregs interact with the microbiota to control inflammation and promote health.

S. Wang et al., MyD88 adaptor-dependent microbial sensing by regulatory T cells promotes mucosal tolerance and enforces commensalism. Immunity 10.1016/j.immuni.2015.06.014 (2015). [Abstract]

Navigate This Article