Transcription Factor Tox2 is required for Follicular Helper T Cells differentiation

Follicular helper T (Tfh) cells are crucial for formation of B cell germinal center (GC) and long-term production of antigen-specific antibodies. The molecular mechanism underlying Tfh cell differentiation, however, still remains largely unknown. Here, we show that the transcription factor Thymocyte selection-associated high mobility group box family member 2 (Tox2) is important for Tfh cell development. Tox2 deficiency led to impaired Tfh cell differentiation and subsequently reduced GC formation. Consistently, ectopic expression of Tox2 promoted Tfh cell differentiation. Mechanistically, we found that Tox2 regulated the expression of Ascl2, an initiator in driving CXCR5 transcription in Tfh cells; Tox2 deficiency caused the decreased expression of Ascl2. Restoration of Ascl2 expression in Tox2 deficient CD4+ T cells rescued the defect in Tfh cell differentiation. Our study suggests that Tox2 is an important transcription factor for Tfh cell development. WT OT-II or Tox2-/- SMARTA mice were transferred into Ly5.1 mice, followed by LCMV infection. Spleens were harvested 7 dpi to sort. For RNAseq, We have four samples, wt-Tfh, ko-Tfh, wt-nonTfh and ko-nonTfh and 2 replicates for Tfh sample.