The transcription factor Zfp281 serves redundantly with Zfp148 to support CD4+ T cell development and functions [Papain multiome]
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. Overall design: Anesthetized mice were injected intranasally with 40 ug of papain suspended in 20 ?l of PBS once per day over two 3-day periods separated by a 10-day rest, and analyzed on day 16 after the initial injection. CD44hiCD4+ cells were sorted from dLN of papain treated mice and prepared for Chromium NextGem Multiome ATAC + Gene Expression by following the 10X protocol for nuclei isolation with a lysis time of 3 minutes.