Zbtb20 identifies and controls a thymus-derived population of regulatory T cells that play a role in intestinal homeostasis

Abstract

The expression of BTB-ZF transcription factors such as ThPOK in CD4 + T cells, Bcl6 in T follicular helper cells, and PLZF in natural killer T cells defines the fundamental nature and characteristics of these cells. Screening for lineage-defining BTB-ZF genes led to the discovery of a subset of T cells that expressed Zbtb20. About half of Zbtb20 + T cells expressed FoxP3, the lineage-defining transcription factor for regulatory T cells (T regs ). Zbtb20 + T regs were phenotypically and genetically distinct from the larger conventional T reg population. Zbtb20 + T regs constitutively expressed mRNA for interleukin-10 and produced high levels of the cytokine upon primary activation. Zbtb20 + T regs were enriched in the intestine and specifically expanded when inflammation was induced by the use of dextran sodium sulfate. Conditional deletion of Zbtb20 in T cells resulted in a loss of intestinal epithelial barrier integrity. Consequently, knockout (KO) mice were acutely sensitive to colitis and often died because of the disease. Adoptive transfer of Zbtb20 + T regs protected the Zbtb20 conditional KO mice from severe colitis and death, whereas non-Zbtb20 T regs did not. Zbtb20 was detected in CD24 hi double-positive and CD62L lo CD4 single-positive thymocytes, suggesting that expression of the transcription factor and the phenotype of these cells were induced during thymic development. However, Zbtb20 expression was not induced in “conventional” T regs by activation in vitro or in vivo. Thus, Zbtb20 expression identified and controlled the function of a distinct subset of T regs that are involved in intestinal homeostasis.

Characterizing control of memory CD8 T cell differentiation by BTB-ZF transcription factor Zbtb20

“…Importantly, numerous BTB-ZF proteins are key factors in CD4 and CD8 T cell development and function (Cheng et al, 2021). To date, studies on Zbtb20 in lymphocytes other than CD8 T cells have determined that Zbtb20 is essential for B cell differentiation into plasma cells (Chevrier et al, 2014) and for a population of IL-10 producing regulatory T cells (Krzyzanowska et al, 2022). However, few direct genomic targets of Zbtb20 are described (Xie et al, 2008;Zhang et al, 2012;Liu et al, 2013Liu et al, , 2017Qu et al, 2016) and no direct targets are described in CD8 T cells, confounding efforts to fully characterize the mechanism(s) through which Zbtb20 controls lymphocytes.…”

ZBTB20 mediates stress‐induced visceral hypersensitivity via activating the NF‐κB/transient receptor potential channel pathway

“…Enteric IPANs, which receive stimulus and function as nociceptors, have similar features like DRG neurons (e.g., sharing typical peptides including substance P and CGRP), and connect closely within ENS network 51 . In addition, we noted that some cells in the interstitium also express ZBTB20, which we speculate might be immunocytes 52 . Taken together, ZBTB20 could contribute to IBS pathogenesis through direct activation of enteric nervous system or immunocytes in peripheral tissues, which remains to be explored in the further research.…”

“…51 In addition, we noted that some cells in the interstitium also express ZBTB20, which we speculate might be immunocytes. 52 Taken together, ZBTB20 could contribute to IBS pathogenesis through direct activation of enteric nervous system or immunocytes in peripheral tissues, which remains to be explored in the further research.…”

Differential Correlation of Transcriptome Data Reveals Gene Pairs and Pathways Involved in Treatment of Citrobacter rodentium Infection with Bioactive Punicalagin

“…The gene Siglec1 is mostly known as a viral receptor but also T cell and apoptotic functions; while Zbtb20 plays roles in lipid homeostasis, negative regulation of transcription, and the regulation of multiple cytokines. The link between the genes may be due to interaction in the intestine with T cells [23]. The last gene-gene pair of Folr2 and Sult1a1 have functions that indicate that punicalagin treatment impacts metabolic features correlated with nutrient uptake within the gastrointestinal system [15,17].…”