Kidney GATA3+ regulatory T cells play roles in the convalescence stage after antibody-mediated renal injury

Abstract

FoxP3+ regulatory T cells (Tregs) play crucial roles in peripheral immune tolerance. In addition, Tregs that reside or accumulate in nonlymphoid tissues, called tissue Tregs, exhibit tissue-specific functions and contribute to the maintenance of tissue homeostasis and repair. In an experimental mouse model of crescentic glomerulonephritis induced by an anti-glomerular basement membrane antibody, Tregs started to accumulate in the kidney on day 10 of disease onset and remained at high levels (~30–35% of CD4+ T cells) during the late stage (days 21–90), which correlated with stable disease control. Treg depletion on day 21 resulted in the relapse of renal dysfunction and an increase in Th1 cells, suggesting that Tregs are essential for disease control during the convalescence stage. The Tregs that accumulated in the kidney showed tissue Treg phenotypes, including high expression of GATA3, ST2 (the IL33 receptor subunit), amphiregulin (Areg), and PPARγ. Although T-bet+ Tregs and RORγt+ Tregs were observed in the kidney, GATA3+ Tregs were predominant during the convalescence stage, and a PPARγ agonist enhanced the accumulation of GATA3+ Tregs in the kidney. To understand the function of specific genes in kidney Tregs, we developed a novel T cell transfer system to T cell-deficient mice. This experiment demonstrates that ST2, Areg, and CCR4 in Tregs play important roles in the accumulation of GATA3+ Tregs in the kidney and in the amelioration of renal injury. Our data suggest that GATA3 is important for the recruitment of Tregs into the kidney, which is necessary for convalescence after renal tissue destruction.

Myeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression via Regulation of CCL5-CCR5 Axis

“…The balance between T H 1 and Treg cells has drawn great attention in cancer (36), various inflammatory diseases (37,38), and autoimmunity diseases (39). Treg accumulation and T H 1 cell downregulation are also necessary for the convalescence of crescentic glomerulonephritis (40). In our study, both in vitro-or in vivo-induced MDSCs promoted MDSC and Treg infiltration in the kidney and downregulated the total CD4 + T and T H 1 cell infiltration in the kidney.…”

Single-Cell Analysis Revealed the Role of CD8+ Effector T Cells in Preventing Cardioprotective Macrophage Differentiation in the Early Phase of Heart Failure

“…Each mouse was deeply anesthetized and intracardially perfused with 40 mL of ice-cold PBS to exclude blood cells. The heart was dissected, minced with fine scissors, and then enzymatically digested with a cocktail of type II collagenase (Worthington), elastase (Worthington), and DNase I (Roche Diagnostics) for one hour at 37°C with gentle agitation as described elsewhere ( 33 ). After digestion, the tissue was triturated and passed through a 70-µm cell strainer.…”

The fellowship of regulatory and tissue-resident memory cells

“…GATA3-expressing Tregs make up over 50% of the Treg cells present, their depletion resulting in increased disease severity. Co-transfer of conventional T cells, including Tregs, into T cell-deficient mice reduced disease severity, while co-transfer with GATA3-deficient Tregs did not suppress disease activity, indicating that type 2-associated gene programme in Treg cells is capable of supressing disease pathology 47 .…”