Transcriptional regulation of IL 10 in T helper cells

IL-10 produced by CD4 T cells plays an essential role in limiting inflammation and autoimmunity. All T help cell subsets can co-produce IL-10 to mitigate unwanted immunopathology but naïve CD4 T cells can also be directly polarized to IL-10 producing Type 1 regulatory (Tr1) cells by the immunoregulatory cytokine, IL-27. Although several transcription factors (TFs) have been shown to regulate IL-10 expression in different contexts, a comprehensive transcriptional network that induce and maintain IL-10 in various CD4 T cells is lacking.Here we utilized two complementary approaches to systemically study the transcriptional mechanisms driving IL-10 production in T helper cells: 1) We combined novel computational tools with transcriptomic profiling of in-vitro Tr1 cell differentiation at high temporal resolution to build a comprehensive and dynamic transcriptional network that regulates IL-10 production in CD4 T cells …