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Zbtb20 identifies and controls a thymus-derived population of regulatory T cells that play a role in intestinal homeostasis
Science Immunology ( IF 24.8 ) Pub Date : 2022-05-06 , DOI: 10.1126/sciimmunol.abf3717
Agata K Krzyzanowska 1, 2 , Rashade A H Haynes Ii 1 , Damian Kovalovsky 3 , Hsin-Ching Lin 1 , Louis Osorio 1 , Karen L Edelblum 4 , Lynn M Corcoran 5 , Arnold B Rabson 1, 2, 6 , Lisa K Denzin 1, 2, 6 , Derek B Sant'Angelo 1, 2, 6
Affiliation  

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.

中文翻译:

Zbtb20 识别和控制胸腺衍生的调节性 T 细胞群,这些细胞在肠道稳态中发挥作用

CD4中ThPOK等BTB-ZF转录因子的表达+T 细胞、T 滤泡辅助细胞中的 Bcl6 和自然杀伤 T 细胞中的 PLZF 定义了这些细胞的基本性质和特征。谱系定义 BTB-ZF 基因的筛选导致发现了表达 Zbtb20 的 T 细胞子集。Zbtb20的一半左右+T 细胞表达 FoxP3,调节性 T 细胞的谱系定义转录因子(T规则). ZBTB20+规则在表型和遗传上与较大的常规 T 不同注册人口。ZBTB20+规则组成型表达白介素 10 的 mRNA,并在初级激活后产生高水平的细胞因子。ZBTB20+规则当使用葡聚糖硫酸钠诱导炎症时,它们在肠道中富集并且特别扩张。条件删除ZBTB20在 T 细胞中导致肠上皮屏障完整性的丧失。因此,敲除 (KO) 小鼠对结肠炎非常敏感,并且经常死于这种疾病。Zbtb20 的过继转移+规则保护 Zbtb20 条件性 KO 小鼠免受严重结肠炎和死亡,而非 Zbtb20 T规则没有。在 CD24 中检测到 Zbtb20你好双阳性和CD62LCD4 单阳性胸腺细胞,表明转录因子的表达和这些细胞的表型在胸腺发育过程中被诱导。然而,Zbtb20 表达在“常规”T 中未被诱导规则通过体外或体内激活。因此,Zbtb20 表达识别并控制了 T 的一个不同子集的功能规则参与肠道稳态。
更新日期:2022-05-06
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