Helicobacter species are potent drivers of colonic T cell responses in homeostasis and inflammation

幽门螺杆菌是稳态和炎症中结肠 T 细胞反应的强大驱动因素

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作者:Jiani N Chai, Yangqing Peng, Sunaina Rengarajan, Benjamin D Solomon, Teresa L Ai, Zeli Shen, Justin S A Perry, Kathryn A Knoop, Takeshi Tanoue, Seiko Narushima, Kenya Honda, Charles O Elson, Rodney D Newberry, Thaddeus S Stappenbeck, Andrew L Kau, Daniel A Peterson, James G Fox, Chyi-Song Hsieh

Abstract

Specific gut commensal bacteria improve host health by eliciting mutualistic regulatory T (Treg) cell responses. However, the bacteria that induce effector T (Teff) cells during inflammation are unclear. We addressed this by analyzing bacterial-reactive T cell receptor (TCR) transgenic cells and TCR repertoires in a murine colitis model. Unexpectedly, we found that mucosal-associated Helicobacter species triggered both Treg cell responses during homeostasis and Teff cell responses during colitis, as suggested by an increased overlap between the Teff/Treg TCR repertoires with colitis. Four of six Treg TCRs tested recognized mucosal-associated Helicobacter species in vitro and in vivo. By contrast, the marked expansion of luminal Bacteroides species seen during colitis did not trigger a commensurate Teff cell response. Unlike other Treg cell-inducing bacteria, Helicobacter species are known pathobionts and cause disease in immunodeficient mice. Thus, our study suggests a model in which mucosal bacteria elicit context-dependent Treg or Teff cell responses to facilitate intestinal tolerance or inflammation.

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