T helper cell trafficking in autoimmune kidney diseases

Abstract

CD4+ T cells are key drivers of autoimmune diseases, including crescentic GN. Many effector mechanisms employed by T cells to mediate renal damage and repair, such as local cytokine production, depend on their presence at the site of inflammation. Therefore, the mechanisms regulating the renal CD4+ T cell infiltrate are of central importance. From a conceptual point of view, there are four distinct factors that can regulate the abundance of T cells in the kidney: (1) T cell infiltration, (2) T cell proliferation, (3) T cell death and (4) T cell retention/egress. While a substantial amount of data on the recruitment of T cells to the kidneys in crescentic GN have accumulated over the last decade, the roles of T cell proliferation and death in the kidney in crescentic GN is less well characterized. However, the findings from the data available so far do not indicate a major role of these processes. More importantly, the molecular mechanisms underlying both egress and retention of T cells from/in peripheral tissues, such as the kidney, are unknown. Here, we review the current knowledge of mechanisms and functions of T cell migration in renal autoimmune diseases with a special focus on chemokines and their receptors.

Altered Circulating Follicular T Helper Cell Subsets and Follicular T Regulatory Cells Are Indicators of a Derailed B Cell Response in Lupus, Which Could Be Modified by Targeting IL-21R

“…Blood T FH 17-like cells seem to share many features with genuine Th17 cells, including their IL-17 and IL-21 cytokine, RORγt transcription factor, as well as CCR6 chemokine receptor expression. There are several investigations that observed the recruitment of circulating CCR6 + Th17 or cT FH cells in response to chemokine ligand production in kidney tissues [ 55 , 56 , 57 , 58 , 59 ]. In a murine lupus model, the inhibition of a multifunctional serine/threonine kinase, namely, calcium/calmodulin-dependent protein kinase IV (CaMK4), led to the decrease in CCR6 and CCL20 expression, as well as to the amelioration of glomerular injury, which highlighted the role of the CCR6/CCL20 axis in SLE [ 60 ].…”

Kidney organoid systems for studies of immune-mediated kidney diseases: challenges and opportunities

“…Besides circulating immune complexes and autoantibodies, dysregulated T cell responses mediate severe inflammation and tissue damage in autoimmune kidney diseases (Riedel et al 2021 ). CD4 + T cells have been shown to drive rapid progressive glomerulonephritis as seen in ANCA-associated glomerulonephritis, anti-GBM nephritis, and lupus nephritis.…”

“…CD4 + T cells have been shown to drive rapid progressive glomerulonephritis as seen in ANCA-associated glomerulonephritis, anti-GBM nephritis, and lupus nephritis. Especially the role of IL-17 producing CD4 + T H 17 cells has gained increasing attention in kidney inflammation (Krebs et al 2017 ; Krebs and Panzer 2018 ; Krohn et al 2018 ; Riedel et al 2021 ). An increased T H 17 response is associated with a more severe course of glomerulonephritis and tubulointerstitial injury (Krebs et al 2017 ).…”

Immune-mediated glomerular diseases: new basic concepts and clinical implications

“…Many effector mechanisms employed by T cells to mediate renal damage and repair, such as local cytokine production, depend on their presence at the site of inflammation. In their article “ T helper cell trafficking in renal inflammation” ( 2021 in this issue) Riedel et al discuss the current knowledge of mechanisms and functions of T cell migration in renal autoimmune diseases with a special focus on chemokines and their receptors.…”