New insights into the mechanisms of Treg function

Abstract

Purpose of review CD4+Foxp3+ regulatory T cells (Tregs) are crucial in controlling immunity and self-tolerance. Consequently, in transplantation, Tregs play a central role in inhibiting acute rejection and promoting allograft tolerance. A more complete understanding of Treg biology may lead to novel therapeutic approaches to enhance Treg numbers and function. Recent findings The maintenance of self-tolerance in non-lymphoid tissues requires the differentiation of Tregs in secondary lymphoid organs from naïve-like central Tregs into effector Tregs. Antigen and environmental cues guide this Treg differentiation, which parallels the types of adaptive immune responses taking place, allowing them to enter and function within specific non-lymphoid tissues. In addition to controlling inflammation, tissue-infiltrating Tregs unexpectedly regulate non-immune processes, including metabolic homeostasis and tissue repair. Finally, Tregs can be directly and specifically targeted in vivo to augment their numbers or enhance their function in both secondary lymphoid organs and non-lymphoid tissues. Summary Tregs exhibit a previously unrecognized breadth of function, which includes tissue-specific specialization and the regulation of both immune and non-immune processes. This is of particular importance in transplantation since allo-reactive memory T cells can act directly within the allograft. Thus, therapeutic approaches may need to promote Treg function in transplanted tissue as well as in secondary lymphoid organs. Such therapy would not only prevent inflammation and acute rejection, but may also promote non-immune processes within the allograft such as tissue homeostasis and repair.

Clinical significance of weak interleukin‐35 expression in patients with psoriasis

“…Moreover, Th17 and T reg cells, which are strongly expressed in the peripheral circulation and skin tissues of patients with psoriasis, are both positively correlated with the PASI . T reg are regulatory T cells that play a dominant role in maintaining immune tolerance, they mainly produces cytokines such as TGF‐β and IL‐10 and can inhibit the functions of other pathogenic Th1 cells (mainly release of IFN‐γ) and Th17 cells (mainly release of IL‐17 and IL‐23), thus limiting development of chronic inflammatory disease and autoimmune disease, as previously reported . However, the relationship between the functions of Th17 and its related cytokines, such as IL‐17 and IL‐23, and T reg cells remains unknown.…”

Irradiation before and donor splenocyte infusion immediately after transplantation induce tolerance to lung, but not heart allografts in miniature swine

“…While heart transplant recipient animals possess higher numbers of pro‐effector lymphocyte phenotypes, lung transplant recipients show a trend towards proregulatory cell types. These findings may further underline the importance of protolerogenic regulatory lymphocytes for the onset of allograft tolerance, which has widely been recognized in rodent, large animal as well as human studies .…”

Blocking CD226 Promotes Allogeneic Transplant Immune Tolerance and Improves Skin Graft Survival by Increasing the Frequency of Regulatory T Cells in a Murine Model

“…Consequently, Tregs play a central role in inhibiting rejection and promoting allograft tolerance during transplantation. A more complete understanding of Treg biology may lead to novel therapeutic approaches to enhance Treg numbers and function [20]. In recent years, CD4 usage in allograft rejection therapies.…”