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Immunol."],"abstract":"<jats:p>\u03b3\u03b4 T cells play important roles in immune responses by rapidly producing large quantities of cytokines. Recently, \u03b3\u03b4 T cells have been found to be involved in tissue homeostatic regulation, playing roles in thermogenesis, bone regeneration and synaptic plasticity. Nonetheless, the mechanisms involved in \u03b3\u03b4 T-cell development, especially the regulation of TCR\u03b4 gene transcription, have not yet been clarified. Previous studies have established that NOTCH1 signaling plays an important role in the<jats:italic>Tcrg<\/jats:italic>and<jats:italic>Tcrd<\/jats:italic>germline transcriptional regulation induced by enhancer activation, which is mediated through the recruitment of RUNX1 and MYB. In addition, interleukin-7 signaling has been shown to be required for<jats:italic>Tcrg<\/jats:italic>germline transcription, V\u03b3J\u03b3 rearrangement and \u03b3\u03b4 T-lymphocyte generation as well as for promoting T-cell survival. In this study, we discovered that interleukin-7 is required for the activation of enhancer-dependent<jats:italic>Tcrd<\/jats:italic>germline transcription during thymocyte development. These results indicate that the activation of both<jats:italic>Tcrg<\/jats:italic>and<jats:italic>Tcrd<\/jats:italic>enhancers during \u03b3\u03b4 T-cell development in the thymus depends on the same NOTCH1- and interleukin-7-mediated signaling pathways. Understanding the regulation of the<jats:italic>Tcrd<\/jats:italic>enhancer during thymocyte development might lead to a better understanding of the enhancer-dependent mechanisms involved in the genomic instability and chromosomal translocations that cause leukemia.<\/jats:p>","DOI":"10.3389\/fimmu.2022.943510","type":"journal-article","created":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T06:59:10Z","timestamp":1660892350000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Interleukin-7 receptor signaling is crucial for enhancer-dependent TCR\u03b4 germline transcription mediated through STAT5 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