Citation

The genome organizer special AT-rich sequence binding protein 1 (SATB1) regulates specific functions through chromatin remodeling in helper T cells. We recently reported that T cells from SATB1 conditional knockout (SATB1cKO) mice, in which the Satb1 gene is deleted from hematopoietic cells, impaired the phosphorylation of signaling molecules in response to T cell receptor (TCR) crosslinking. However, the in vivo T cell response upon antigen presentation in the absence of SATB1 remains unclear. We show that SATB1 modulates the T cell antigen response during the induction and effector phases. The expression of SATB1 was upregulated in response to TCR stimulation, suggesting that SATB1 is important for the antigen response. Therefore, we examined the role of SATB1 in the TCR response and induced experimental autoimmune encephalomyelitis (EAE) using the myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55) and pertussis toxin. SATB1cKO mice were resistant to EAE and showed defects in IL-17- and IFN-producing pathogenic T cells. Thus, SATB1 expression appears necessary for T cell function in the induction phase. To examine SATB1 function during the effector phase, we used a tamoxifen-inducible SATB1 deletion system, SATB1cKO-ER-Cre mice. We transferred encephalitogenic T cells from MOG35-55-immunized SATB1cKO-ER-Cre mice into healthy mice. Tamoxifen-treated recipient mice before the onset of paralysis were resistant to EAE. Furthermore, recipient mice treated with tamoxifen after the onset of EAE exhibited no disease progression. Thus, SATB1 is essential for maintaining TCR responsiveness during the induction and effector phases and may represent a novel therapeutic target for T cell-mediated autoimmune diseases. 2018 The Societies and John Wiley & Sons Australia, Ltd.