Satb1 directs the differentiation of TH17 cells through suppression of IL-2 expression

Abstract

T helper (T_H)17 cells are crucial for host defense in barrier organs, and their altered functionality can disrupt tissue homeostasis, increasing the risk of autoimmune diseases. Thus, it is essential to understand the mechanisms controlling T_H17 differentiation to develop strategies influencing their role in diseases. Here, we identified Special AT-rich sequence-binding protein 1 (Satb1) as a pioneering factor for T_H17 development. Satb1 is highly expressed in T_H17 cells, and loss of Satb1 prevents the differentiation of T_H17 cells. Consequently, expression of Satb1 in CD4⁺ T cells is required for the formation of T_H17-driven autoimmune diseases. Mechanistically, Satb1 mediates T_H17 development through regulating accessibility of the Il2 gene locus and thereby preventing interleukin (IL)-2 signaling early during T_H17 differentiation. Hence, suppression of IL-2 expression by Satb1 during T_H17 formation is pivotal, suggesting that Satb1 could serve as a novel therapeutic target for treating autoimmune diseases driven by T_H17 cells.

Keywords: CD4(+) T cell differentiation; CP: Immunology; EAE; IL-2; Satb1; T(H)17 cells; autoimmune disease; colitis; scRNA-seq; single-cell MultiOMICs.