The transcription factor Zfp281 serves redundantly with Zfp148 to support CD4+ T cell development and functions [Thymus Visium]
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: Tissue sections from FFPE fixed thymi from C5YBL/6 and tdKO mice were first destained and decrosslinked according to the 10X Demonstrated Protocol CG000520.  Probe hybridization and all subsequent steps were performed as per 10X User guide for Visium CytAssist Spatial Gene Expression (CG000495). In brief, probe hybridization was performed overnight on the destained and decrosslinked tissue sections followed by probe ligation, and CytAssist enabled RNA digestion and tissue removal. Subsequently, probe extension was carried out and the ligation product was eluted, and a pre-amplification step performed. A subset of the pre-amplification product was used for library construction. Quality and concentration of the resulting sequencing library was checked using Bioanalyzer instrument (Agilent 2100).