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Target Concepts:
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Query: UMLS:C0014070 (
encephalomyelitis
)
13,017
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The
SWI
/SNF chromatin-remodeling complex has been implicated in the activation and proliferation of T cells. After T cell receptor signaling, the
SWI
/SNF complex rapidly associates with chromatin and controls gene expression in T cells. However, the process by which the
SWI
/SNF complex regulates peripheral T cell activation has not been elucidated. In this study, we show that the
SWI
/SNF complex regulates cytokine production and proliferation of T cells. During T cell activation, the
SWI
/SNF complex is recruited to the promoter of the transcription factor AP-1, and it increases the expression of AP-1. Increased expression of the
SWI
/SNF complex resulted in enhanced AP-1 activity, cytokine production, and proliferation of peripheral T cells, whereas knockdown of the
SWI
/SNF complex expression impaired the AP-1 expression and reduced the activation and proliferation of T cells. Moreover, mice that constitutively expressed the
SWI
/SNF complex in T cells were much more susceptible to experimentally induced autoimmune
encephalomyelitis
than the normal mice were. These results suggest that the
SWI
/SNF complex plays a critical role during T cell activation and subsequent immune responses.
...
PMID:The SWI/SNF chromatin-remodeling complex modulates peripheral T cell activation and proliferation by controlling AP-1 expression. 1991 Apr 61
The physiological functions of members of the tumor-necrosis factor (TNF) receptor (TNFR)-associated factor (TRAF) family in T cell immunity are not well understood. We found that in the presence of interleukin 6 (IL-6), naive TRAF5-deficient CD4(+) T cells showed an enhanced ability to differentiate into the TH17 subset of helper T cells. Accordingly, TH17 cell-associated experimental autoimmune
encephalomyelitis
(EAE) was greatly exaggerated in Traf5(-/-) mice. Although it is normally linked with TNFR signaling pathways, TRAF5 constitutively associated with a cytoplasmic region in the signal-transducing receptor gp130 that overlaps with the binding site for the
transcription activator
STAT3 and suppressed the recruitment and activation of STAT3 in response to IL-6. Our results identify TRAF5 as a negative regulator of the IL-6 receptor signaling pathway that limits the induction of proinflammatory CD4(+) T cells that require IL-6 for their development.
...
PMID:The adaptor TRAF5 limits the differentiation of inflammatory CD4(+) T cells by antagonizing signaling via the receptor for IL-6. 2468 64
T
H
17 cells originating from regulatory T (T
reg
) cells upon loss of the T
reg-
specific transcription factor Foxp3 accumulate in sites of inflammation and aggravate autoimmune diseases. Whether an active mechanism drives the generation of these pathogenic 'ex-Foxp3 T
H
17' cells, remains unclear. Here we show that pro-inflammatory cytokines enhance the expression of transcription regulator Id2, which mediates cellular plasticity of T
reg
into ex-Foxp3 T
H
17 cells. Expression of Id2 in in vitro differentiated iT
reg
cells reduces the expression of Foxp3 by sequestration of the
transcription activator
E2A, leading to the induction of T
H
17-related cytokines. T
reg
-specific ectopic expression of Id2 in mice significantly reduces the T
reg
compartment and causes immune dysregulation. Cellular fate-mapping experiments reveal enhanced T
reg
plasticity compared to wild-type, resulting in exacerbated experimental autoimmune
encephalomyelitis
pathogenesis or enhanced anti-tumor immunity. Our findings suggest that controlling Id2 expression may provide a novel approach for effective T
reg
cell immunotherapies for both autoimmunity and cancer.
...
PMID:Inflammation-induced Id2 promotes plasticity in regulatory T cells. 3041 14
