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

Krzyzanowska, AK; Haynes Ii, RAH; Kovalovsky, D; Lin, HC; Osorio, L; Edelblum, KL; Corcoran, LM; Rabson, AB; Denzin, LK; Sant&#39;Angelo, DB

Author(s): Krzyzanowska, AK; Haynes Ii, RAH; Kovalovsky, D; Lin, HC; Osorio, L; Edelblum, KL; Corcoran, LM; Rabson, AB; Denzin, LK; Sant'Angelo, DB;
Details: Publication Year 2022-05-06,Volume 7,Issue #71,Page eabf3717
Journal Title: Science Immunology
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.
Publisher: AAAS
Keywords: Animals; *Colitis/chemically induced; Forkhead Transcription Factors/genetics; Homeostasis; Intestines; Mice; Mice, Knockout; *T-Lymphocytes, Regulatory/metabolism; Transcription Factors
Research Division(s): Immunology
PubMed ID: 35522722
Publisher's Version: https://doi.org/10.1126/sciimmunol.abf3717
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2022-05-11 10:50:31

Last Modified: 2022-05-11 11:23:24