CD4⁺ T‐cell subsets in intestinal inflammation

Abstract

Intestinal CD4+ T cells are essential mediators of immune homeostasis and inflammation. Multiple subsets of CD4+ T cells have been described in the intestine, which represents an important site for the generation and regulation of cells involved in immune responses both within and outside of the gastrointestinal tract. Recent advances have furthered our understanding of the biology of such cells in the intestine. Appreciation of the functional roles for effector and regulatory populations in health and disease has revealed potential translational targets for the treatment of intestinal diseases, including inflammatory bowel disease. Furthermore, the role of dietary and microbiota-derived factors in shaping the intestinal CD4+ T-cell compartment is becoming increasingly understood. Here, we review recent advances in understanding the multifaceted roles of CD4+ T cells in intestinal immunity.

The Cytosolic Microbial Receptor Nod2 Regulates Small Intestinal Crypt Damage and Epithelial Regeneration following T Cell–Induced Enteropathy

“…The requirement of T cells in various animal models of intestinal inflammation (12) and the increase in T cell-derived inflammatory cytokines in the mucosa of inflammatory bowel disease (IBD) patients (17) suggest that T cells play important roles in the pathogenesis of IBD. Our study demonstrates that following small intestinal mucosal damage induced by T cell activation, microbiota sensing by Nod2 is important for controlling immune activation, crypt damage, and epithelial regeneration.…”

“…Although the etiology of CD remains unclear, the high numbers of T cells in the inflamed intestinal mucosa, the secretion of large amounts of T cell-derived proinflammatory cytokines, and the requirement for T cells in various animal models of chronic intestinal inflammation strongly suggest a role of T cells in the pathogenesis of CD (12). Our group previously showed that, although Nod2 is expressed and functionally active in murine CD4 + T cell subsets, the expression of Nod2 is not required for the development or the prevention of the T cell transfer model of colitis in Rag-deficient mice (6).…”

Cyclosporine A Regulates Pro-Inflammatory Cytokine Production in Ulcerative Colitis

“…The decrease in IL-13 production can be explained by the CsA mediated induction of apoptosis. This process plays a crucial role in T cell development and homeostasis (Shale et al 2013). In IBD, LPMCs of patients show a decreased susceptibility to apoptosis which leads to an uncontrolled expansion of effector T cells causing gut inflammation Mudter and Neurath 2007).…”

Tuning mTOR activity for immune balance

“…Intestinal homeostasis arises from a highly dynamic balance between effector T cell responses and regulatory mechanisms, in which Foxp3-expressing Tregs play a central role (12). Park et al asked whether exacerbated inflammation in the absence of TSC1 was also due to defects in the Treg compartment, specifically Foxp3 expression and in vivo suppressive activity (11).…”

“…These results suggest the presence of specific signals during inflammation, especially in the intestine, that sustain TSC1 function in T cells, thereby preventing aberrant mTORC1 activation and dysregulated effector and regulatory T cell responses. Antiinflammatory substances such as TGF-β and retinoic acid (RA) are important in orchestrating the induction of tolerance in the intestine (12). More recently, short-chain fatty acids, a class of microbial metabolites, have been shown to establish colonic homeostasis via the regulation of Treg generation and function (19).…”