Tissue Tregs

Abstract

The immune system is responsible for defending an organism against the myriad of microbial invaders it constantly confronts. It has become increasingly clear that the immune system has a second major function: the maintenance of organismal homeostasis. Foxp3+CD4+ regulatory T cells (Tregs) are important contributors to both of these critical activities, defense being the primary purview of Tregs circulating through lymphoid organs, and homeostasis ensured mainly by their counterparts residing in parenchymal tissues. This review focuses on so-called tissue Tregs. We first survey existing information on the phenotype, function, sustaining factors, and human equivalents of the three best-characterized tissue-Treg populations—those operating in visceral adipose tissue, skeletal muscle, and the colonic lamina propria. We then attempt to distill general principles from this body of work—as concerns the provenance, local adaptation, molecular sustenance, and targets of action of tissue Tregs, in particular.

Unstable FoxP3 + T regulatory cells in NZW mice

“…Treg homeostasis | FoxP3 stability | immunoregulation | inbred mice F oxP3 + T regulatory (Treg) cells help maintain lymphoid homeostasis in many immunological contexts: tolerance to self vs. autoimmune deviation, fetal-maternal tolerance, allergy, responses to pathogens, and interactions with commensal microbes (1)(2)(3). Their importance is highlighted by the devastating multiorgan inflammation of FoxP3-deficient scurfy mice or immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) patients (4).…”

“…Their importance is highlighted by the devastating multiorgan inflammation of FoxP3-deficient scurfy mice or immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) patients (4). In addition, Treg cells partake in extraimmune regulatory activities (3). In keeping with these pleiotropic roles, several pathways and molecular mediators partake in Treg cell function, involving cell-cell interactions, soluble cytokines, or small-molecule mediators (5,6).…”

Immune and myodegenerative pathomechanisms in inclusion body myositis

“…It has become evident that distinct tissue‐specific Treg populations with unique phenotypical and functional properties exist. In skeletal muscle, they arise from a small pool of resident Tregs and strongly accumulate following muscle damage 115, 116. Under the control of interleukin (IL)‐33, these myophil Tregs execute essential functions in promoting and orchestrating local regeneration upon muscle injury 117, 118.…”

“…The physiological role of muscle‐resident Tregs and their contribution during myositis has only begun to unravel. It becomes apparent that few studies so far addressed the presence and subcategorization of CD4 + T cells, including Tregs (which constitute up to 60% of CD4 + T cells in muscle upon injury116), in muscle infiltrates of IBM. Such work could help to better understand the role of these cells.…”

The Role of the Innate and Adaptive Immunity in Exercise Induced Muscle Damage and Repair

“…Importantly the tissue Tregs do not require TCR signals for activation, but instead, rely on the secretion of IL-33 from damaged cells and cytokine signaling for their activation and function to facilitate tissue repair through their ability to secrete amphiregulin [12,52,54]. Therefore tissue Tregs have developed a specialized function in sensing changes in their environment to limit inflammation and promote repair [55].…”