Divergent gene expression in heterogeneous Th17 cells by Satb1 that regulates encephalitogenic potentials in inflammatory responses

The genome organizer, special AT-rich sequence-binding protein-1 (Satb1), plays a pivotal role in the regulation of global gene networks in a cell type-dependent manner and is indispensable for the development of multiple cell types, including mature CD4+ T, CD8+ T, and Foxp3+ regulatory T cells in the thymus. However, it remains unknown how the differentiation and effector program of the Th subsets in the periphery are regulated by Satb1. Here, we demonstrate that Satb1 differentially regulates gene expression profiles in non-pathogenic and pathogenic Th17 cells and promotes the pathogenic effector program of encephalitogenic Th17 cells by regulating GM-CSF and PD-1 expression. However, Satb1 is dispensable for the differentiation and non-pathogenic functions of Th17 cells. These results indicate that the divergent gene expression and heterogeneity of tissue Th17 cells are dynamically altered by Satb1 in an environmental context-dependent manner.