Abstract
Throughout the last years, gut-resident Foxp3+ regulatory T (Treg) cells have been associated with a growing number of tissue-specific functions in the intestine, comprising various aspects of gut immunity and physiology. Treg cells have pivotal roles in intestinal tolerance induction and host defense by actively controlling immune responses towards harmless dietary antigens and commensal microorganisms as well as towards invading pathogens. In addition to these immune-related roles, it has become increasingly clear that intestinal Treg cells also exert important non-immune functions in the gut, such as promoting local tissue repair and preserving the integrity of the epithelial barrier. Thereby, intestinal Treg cells critically contribute to the maintenance of tissue homeostasis. In order to account for this functional diversity, gut-resident Treg cells have specifically adapted to the intestinal tissue microenvironment. In this Review, we discuss the specialization of Treg cells in the intestine. We survey the different populations of gut-resident Treg cells focussing on their unique functions, phenotypes and distinct transcription factor dependencies.
Highlights
One of the major functions of Foxp3+ Treg cells residing in non-lymphoid tissues is to control local inflammation
A very recent report discovered that microbiota-dependent receptor gt (RORgt)+ peripherally-derived Treg (pTreg) cells and immunoglobulin A (IgA)+ B cells can regulate each other in a double-negative feedback loop that is transmitted through multiple generations [54]
Given that RORgt+ pTreg cell differentiation is dependent on c-Maf, these results suggest that the hyper IgA phenotype of Treg cell-specific c-Maf-deficient mice is at least partially driven by the lack of direct suppression of RORgt+ pTreg cells on IgA [32]
Summary
Treg cells have pivotal roles in intestinal tolerance induction and host defense by actively controlling immune responses towards harmless dietary antigens and commensal microorganisms as well as towards invading pathogens. In addition to these immune-related roles, it has become increasingly clear that intestinal Treg cells exert important non-immune functions in the gut, such as promoting local tissue repair and preserving the integrity of the epithelial barrier. In order to account for this functional diversity, gut-resident Treg cells have adapted to the intestinal tissue microenvironment In this Review, we discuss the specialization of Treg cells in the intestine.
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