A T cell-specific deletion of HDAC1 protects against experimental autoimmune encephalomyelitis.

In this study we report that mice with a T cell-specific deletion of HDAC1 (using the Cd4-Cre deleter strain; HDAC1-cKO) were completely resistant to EAE despite the ability of HDAC1cKO CD4(+) T cells to differentiate into Th17 cells. RNA sequencing revealed STAT1 as a prominent upstream regulator of differentially expressed genes in activated HDAC1-cKO CD4(+) T cells and this was accompanied by a strong increase in phosphorylated STAT1 (pSTAT1). This suggests that HDAC1 controls STAT1 activity in activated CD4(+) T cells. Increased pSTAT1 levels correlated with a reduced expression of the chemokine receptors Ccr4 and Ccr6, which are important for the migration of T cells into the CNS. Finally, EAE susceptibility was restored in WT:HDAC1-cKO mixed BM chimeric mice, indicating a cell-autonomous defect. Our data demonstrate a novel pathophysiological role for HDAC1 in EAE and provide evidence that selective inhibition of HDAC1 might be a promising strategy for the treatment of MS.
PMID: 28964722 [PubMed - as supplied by publisher]

Source: Journal of Autoimmunity - September 27, 2017 Category: Allergy & Immunology Authors: Göschl L, Preglej T, Hamminger P, Bonelli M, Andersen L, Boucheron N, Gülich AF, Müller L, Saferding V, Mufazalov IA, Hirahara K, Seiser C, Matthias P, Penz T, Schuster M, Bock C, Waisman A, Steiner G, Ellmeier W Tags: J Autoimmun Source Type: research