Regulatory T cells in renal disease

Abstract

The kidney is vulnerable to injury, both acute and chronic from a variety of immune and metabolic insults, all of which at least to some degree involve inflammation. Regulatory T cells modulate systemic autoimmune and allogenic responses in glomerulonephritis and transplantation. Intrarenal regulatory T cells (Tregs), including those recruited to the kidney, have suppressive effects on both adaptive and innate immune cells, and probably also intrinsic kidney cells. Evidence from autoimmune glomerulonephritis implicates antigen‐specific Tregs in HLA‐mediated dominant protection, while in several human renal diseases Tregs are abnormal in number or phenotype. Experimentally, Tregs can protect the kidney from injury in a variety of renal diseases. Mechanisms of Treg recruitment to the kidney include via the chemokine receptors CCR6 and CXCR3 and potentially, at least in innate injury TLR9. The effects of Tregs may be context dependent, with evidence for roles for immunoregulatory roles both for endogenous Tbet‐expressing Tregs and STAT‐3‐expressing Tregs in experimental glomerulonephritis. Most experimental work and some of the ongoing human trials in renal transplantation have focussed on unfractionated thymically derived Tregs (tTregs). However, induced Tregs (iTregs), type 1 regulatory T (Tr1) cells and in particular antigen‐specific Tregs also have therapeutic potential not only in renal transplantation, but also in other kidney diseases.

CD226 deficiency on regulatory T cells aggravates renal fibrosis via up-regulation of Th2 cytokines through miR-340

“…The kidney is vulnerable to injury by various immune and metabolic insults. Tregs have been shown to play an important role in modulating immune responses in numerous models of renal disease, with evolving evidence suggesting that Tregs are important for maintaining tolerance to auto‐antigens and regulating and repairing renal diseases, particularly CKD and after kidney transplantation . The regulatory effects of Tregs may be applied clinically by expanding Tregs in vivo for use in low‐dose IL‐2 cytokine therapy and other pharmacologic agents (e.g., rapamycin), administering suppressive cytokines produced by Tregs, or inducing Tregs from naïve CD4 + T cells.…”

“…Tregs exert important suppressive and homeostasis effects on cancer, autoimmune disorders, and inflammatory responses . Experimentally, Tregs can protect the kidney from injury in various renal diseases, including autoimmune kidney disease and kidney transplant rejection . Elucidating the factors influencing Treg function is important for understanding the disease pathogenesis and further identifying therapeutic opportunities.…”

The complexity and diversity of major histocompatibility complex challenge disease association studies

“…The conformation of HLA‐DRB1*01 presenting immunodominant autoreactive peptide prefers interaction with regulatory T cells. In coronary artery disease, the increased disease risk mediated by HLA‐DRB1*01 was linked with BTNL2 and their inhibitory effect on regulatory T cell proliferation …”

“…In coronary artery disease, the increased disease risk mediated by HLA-DRB1*01 was linked with BTNL2 and their inhibitory effect on regulatory T cell proliferation. 26,[70][71][72] 5.1 | MHC is a strong risk factor for type 1 diabetes…”

Regulatory T‐cell heterogeneity

“…Alikhan et al 3 discuss how Tregs play a protective role in chronic and acute kidney damage. Alikhan et al 3 discuss how Tregs play a protective role in chronic and acute kidney damage.…”