Type 1 regulatory T cell-mediated tolerance in health and disease

Abstract

Type 1 regulatory T (Tr1) cells, in addition to other regulatory cells, contribute to immunological tolerance to prevent autoimmunity and excessive inflammation. Tr1 cells arise in the periphery upon antigen stimulation in the presence of tolerogenic antigen presenting cells and secrete large amounts of the immunosuppressive cytokine IL-10. The protective role of Tr1 cells in autoimmune diseases and inflammatory bowel disease has been well established, and this led to the exploration of this population as a potential cell therapy. On the other hand, the role of Tr1 cells in infectious disease is not well characterized, thus raising concern that these tolerogenic cells may cause general immune suppression which would prevent pathogen clearance. In this review, we summarize current literature surrounding Tr1-mediated tolerance and its role in health and disease settings including autoimmunity, inflammatory bowel disease, and infectious diseases.

Immune modulation in transplant medicine: a comprehensive review of cell therapy applications and future directions

“…Tr1 cell therapy has shown promising potential in transplantation to improve graft acceptance and patient outcomes, representing a significant step toward more targeted and less toxic immunomodulation strategies ( 37 , 42 ). However, the need for specific Tr1-cell biomarkers, enhanced in vitro expansion techniques, and a deeper understanding of their regulatory mechanisms pose challenges that future research must address to fully harness the therapeutic potential of Tr1 cells in clinical practice.…”

“…It is important to note that not all regulatory T cells express Foxp3 ( 41 ). Type 1 regulatory T (Tr1) cells, for instance, do not express Foxp3 but instead secrete high levels of IL-10 and contribute to immune tolerance primarily through IL-10 and TGF-β dependent pathways, contributing to their regulatory capabilities ( 42 ). Thus, the functional mechanisms of T regs are more diverse than solely suppressive interactions, encompassing a range of anti-inflammatory pathways.…”

“…The potential to tailor Tr1 cells to the specific antigens of the transplanted organ opens a pathway to more personalized and effective transplant therapies, enhancing graft survival while maintaining overall immune system integrity ( 54 ). Clinically, protocols have been developed for the in vitro expansion of Tr1 cells ( 55 , 56 ), enabling their use as therapeutic products in immune-mediated diseases and transplantation ( 42 ). However, challenges remain, such as the need for specific biomarkers to isolate pure Tr1 cells and the limited expansion capacity of current protocols ( 47 ).…”

Lineage origin and transcriptional control of autoantigen-specific T-regulatory type 1 cells

“…In light of these challenges, hampering progress in defining the significance of the TR1 cell subset in both physiology and pathology, extensive efforts were made to better describe the molecular hallmarks of the TR1 subset [Reviewed in ( 17 )]. Notwithstanding the fact that markers strictly unique to TR1 cells remain elusive, recent advances have made it possible to more accurately identify such cells in biological samples.…”

Biomaterial-enhanced treg cell immunotherapy: A promising approach for transplant medicine and autoimmune disease treatment

“…Upon stimulation, these cells can temporarily increase their levels of Foxp3 expression and have demonstrated their ability to sustain tolerance in peripheral tissues, regulate the responses of effector T cells in autoimmune conditions, and hinder the rejection of transplanted organs. The ability to cultivate antigen-specific Tr1 cells in vitro has encouraged their practical application in clinical settings related to transplant medicine and autoimmune diseases [ 29 ].…”