Abstract
CD4+ Tregs need to migrate from the mucosal periphery into the draining lymph node via CCR7 to exert their suppressive effects. In this study, we investigated whether CCR7 deficiency resulted in failure of immune suppression in 2% dextran sulfate sodium-induced colitis. Unexpectedly, intestinal inflammation was not exacerbated in the absence of CCR7. Expression of IL-10, a representative suppressive cytokine, was enhanced in CCR7KO CD8+ T cells. Colon CCR7KO CD8+ T cells reduced the activation of CD4+ T cells. Depletion of CD8+ T cells using anti-CD8 antibody exacerbated colitis in CCR7KO mice. Plasmacytoid dendritic cell numbers were also slightly increased during intestinal inflammation in the absence of CCR7, and the depletion of those cells exacerbated DSS-induced colitis in CCR7KO mice. These results suggest that CD8+ T cells and plasmacytoid dendritic cells have compensatory roles in immune regulation in the gut for impaired function of CD4+ Tregs.
Highlights
In mammals, the highest microbial load in the body is in the digestive tract, which harbors up to 1014 commensal bacteria per gram of fecal matter [1]
We investigated whether chemokine receptor 7 (CCR7) deficiency leads to severe intestinal inflammation in a murine dextran sulfate sodium (DSS)-induced colitis model
Histological examination of colon showed that CCR7-knock out (CCR7KO) mice showed significantly severe inflammatory pathology in absence of CD8+ T cells after DSS treatment (Figure 6c and 6d). Inflammatory innate cells such as neutrophil, macrophages and myeloid dendritic cells in the colon of CCR7KO mice were obviously increased in absence of CD8+ T cells (Figure 6e6g). These results suggested that intestinal inflammation was exacerbated in the CCR7KO mice when CD8+ T cells were depleted the role of CD8+ T cells was ambiguous in the WT mice
Summary
The highest microbial load in the body is in the digestive tract, which harbors up to 1014 commensal bacteria per gram of fecal matter [1]. Commensal microbiota competes with and inhibits pathogens, contributing to the host’s defense against infection [4]. It seems that the gastro-intestinal immune system sustains the intestinal microbiota to maintain a mutually beneficial state of intestinal homeostasis [1]. IBD is a group of inflammatory conditions affecting the small and large intestine in man, including ulcerative colitis (UC) and Crohn’s disease (CD) [6]. This is a complex disease caused by the interaction of environmental and genetic risk factors. Depletion of Foxp3+ Treg exacerbates intestinal inflammation even in the T-cell-independent colitis model [11]
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