Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0014070 (
encephalomyelitis
)
13,017
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Tumor progression locus 2
(
TPL-2
) expression is required for efficient polarization of naive T cells to Th1 effector cells in vitro, as well as for Th1-mediated immune responses. In the present study, we investigated the potential role of
TPL-2
in Th17 cells.
TPL-2
was found to be dispensable for Th17 cell differentiation in vitro, and for the initial priming of Th17 cells in experimental autoimmune
encephalomyelitis
(EAE), a Th17 cell-mediated disease model for multiple sclerosis. Nevertheless,
TPL-2
-deficient mice were protected from EAE, which correlated with reduced immune cell infiltration, demyelination, and axonal damage in the CNS. Adoptive transfer experiments demonstrated that there was no T cell-intrinsic function for
TPL-2
in EAE, and that
TPL-2
signaling was not required in radiation-sensitive hematopoietic cells. Rather,
TPL-2
signaling in radiation-resistant stromal cells promoted the effector phase of the disease. Importantly, using a newly generated mouse strain expressing a kinase-inactive form of
TPL-2
, we demonstrated that stimulation of EAE was dependent on the catalytic activity of
TPL-2
and not its adaptor function to stabilize the associated ubiquitin-binding protein ABIN-2. Our data therefore raise the possibility that small molecule inhibitors of
TPL-2
may be beneficial in multiple sclerosis therapy.
...
PMID:Regulation of experimental autoimmune encephalomyelitis by TPL-2 kinase. 2463 51
