The transcription factor Zfp281 serves redundantly with Zfp148 to support CD4+ T cell development and functions [Population RNA-seq]

The transcription factor Gata3 is essential both for CD4+ T cell development in the thymus and for the differentiation of Th2 cells, which mediate responses against extracellular parasites and contribute to asthma and allergies. Here we report that the transcription factor Zfp281, in part redundantly with its paralog Zfp148, cooperates with Gata3 to promote CD4+ T cell development and Th2 cell differentiation. Disruption of both factors in T cells resulted in reduced numbers of spleen CD4+ T cells. Additionally, we show that Zfp281 interacts with Gata3, and that Zfp281 binds to Th2 cytokine loci in Th2 cells. Finally, we found that Zfp148 and Zfp281 promote Th2 cytokine expression. During airway inflammation, Zfp148/281-deficient CD4+ T cells failed to express Th2 cytokines, despite normal expression of Gata3. Altogether our data identify Zfp148 and Zfp281 as essential for enabling Gata3 functions in both CD4+ T cell development and Th2 function. Thymocytes were sorted for population RNAseq.转录因子Gata3对于胸腺内CD4阳性T细胞（CD4+ T cell）的发育，以及介导抗细胞外寄生虫免疫应答、参与哮喘与过敏反应发生的Th2细胞（Th2 cell）的分化均具有不可或缺的作用。本研究报道，转录因子Zfp281与其旁系同源基因Zfp148存在部分功能冗余，可与Gata3协同促进CD4阳性T细胞发育与Th2细胞分化。在T细胞中同时敲除这两个因子，会导致脾脏CD4阳性T细胞数量显著减少。此外，本研究证实Zfp281可与Gata3发生相互作用，且Zfp281能够结合Th2细胞中的Th2细胞因子基因座。最后，本研究发现Zfp148与Zfp281可促进Th2细胞因子的表达。在气道炎症过程中，尽管Gata3的表达水平正常，但Zfp148与Zfp281双缺陷型CD4阳性T细胞无法正常表达Th2细胞因子。综上，本研究数据证实Zfp148与Zfp281是Gata3在CD4阳性T细胞发育及Th2细胞功能中发挥正常功能的必需调控因子。本研究通过分选胸腺细胞以开展群体RNA测序（RNA-seq）。