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Special AT-rich sequence binding protein 1 is required for maintenance of T cell
receptor responsiveness and development of experimental autoimmune
encephalomyelitis
#MMPMID29388727
Akiba Y
; Kuwabara T
; Mukozu T
; Mikami T
; Kondo M
Microbiol Immunol
2018[Apr]; 62
(4
): 255-268
PMID29388727
show ga
The genome organizer special AT-rich sequence binding protein 1 (SATB1) regulates
specific functions through chromatin remodeling in T helper cells. It was
recently reported by our team that T cells from SATB1 conditional knockout
(SATB1cKO) mice, in which the Satb1 gene is deleted from hematopoietic cells,
impair phosphorylation of signaling molecules in response to T cell receptor
(TCR) crosslinking. However, in vivo T cell responses upon antigen presentation
in the absence of SATB1 remain unclear. In the current study, it was shown that
SATB1 modulates T cell antigen responses during the induction and effector
phases. Expression of SATB1 was upregulated in response to TCR stimulation,
suggesting that SATB1 is important for this antigen response. The role of SATB1
in TCR responses and induced experimental autoimmune encephalomyelitis (EAE) was
therefore examined using the myelin oligodendrocyte glycoprotein peptide 35-55
(MOG35-55) and pertussis toxin. SATB1cKO mice were found to be resistant to EAE
and had 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, a tamoxifen-inducible SATB1
deletion system, SATB1cKO-ER-Cre mice, was used. Encephalitogenic T cells from
MOG35-55-immunized SATB1cKO-ER-Cre mice were transferred into healthy mice. Mice
that received tamoxifen before the onset of paralysis were resistant to EAE.
Furthermore, no disease progression occurred in recipient mice treated with
tamoxifen after the onset of EAE. Thus, SATB1 is essential for maintaining TCR
responsiveness during the induction and effector phases and may provide a novel
therapeutic target for T cell-mediated autoimmune diseases.
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