Chromatin remodeling by the SWI/SNF-like BAF complex and STAT4 activation synergistically induce IL-12Rβ2 expression during human Th1 cell differentiation

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Abstract
Interleukin‐12 (IL‐12) is a key cytokine for the development of T helper type 1 (Th1) responses; however, naïve CD4+ T cells do not express IL‐12Rβ2, and are therefore unresponsive to IL‐12. We have examined the mechanisms that control Th1‐specific expression of the human IL‐12Rβ2 gene at early time points after T‐cell stimulation. We have identified a Th1‐specific enhancer element that binds signal transducer and activator of transcription 4 (STAT4) in vivo in developing Th1 but not Th2 cells. T‐cell receptor (TCR) signaling induced histone hyperacetylation and recruitment of BRG1, the ATPase subunit of the SWI/SNF‐like BAF chromatin remodeling complex, to the IL‐12Rβ2 regulatory regions and was associated with low‐level gene transcription at the IL‐12Rβ2 locus. However, high‐level IL‐12Rβ2 expression required TCR triggering in the presence of IL‐12. Our results indicate a synergistic role of TCR‐induced chromatin remodeling and cytokine‐induced STAT4 activation to direct IL‐12Rβ2 expression during Th1 cell development.