Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Surface molecules that are differentially expressed on Th1 and Th2 cells may be useful in regulating specific immune responses in vivo. Using a panel of mAbs, we have identified murine CD226 as specifically expressed on the surface of differentiated Th1 cells but not Th2 or Th0 cells. Although CD226 is constitutively expressed on CD8 cells, it is up-regulated on CD4 cells upon activation. Th1 differentiation results in enhanced CD226 expression, whereas expression is down-regulated upon Th2 polarization. We demonstrate that CD226 is involved in the regulation of T cell activation; in vivo treatment with anti-CD226 results in significant reduction of Th1 cell expansion and in the induction of APCs that inhibit T cell activation. Furthermore, anti-CD226 treatment delays the onset and reduces the severity of a Th1-mediated autoimmune disease, experimental autoimmune encephalomyelitis. Our data suggest that CD226 is a costimulatory molecule that plays an important role in activation and effector functions of Th1 cells.
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PMID:CD226 is specifically expressed on the surface of Th1 cells and regulates their expansion and effector functions. 1654 12

Recent association studies have linked numerous genetic variants with an increased risk for multiple sclerosis, although their functional relevance remains largely unknown. Here we investigated phenotypical and functional consequences of a genetic variant in the CD226 gene that, among other autoimmune diseases, predisposes to multiple sclerosis. Phenotypically, effector and regulatory CD4(+) memory T cells of healthy individuals carrying the predisposing CD226 genetic variant showed, in comparison to carriers of the protective variant, reduced surface expression of CD226 and an impaired induction of CD226 after stimulation. This haplotype-dependent reduction in CD226 expression on memory T cells was abrogated in patients with multiple sclerosis, as CD226 expression was comparable to healthy risk haplotype carriers irrespective of genetic variant. Functionally, FOXP3-positive regulatory T cells from healthy carriers of the genetic protective variant showed superior suppressive capacity, which was again abrogated in multiple sclerosis patients. Mimicking the phenotype of human CD226 genetic risk variant carriers, regulatory T cells derived from Cd226-deficient mice showed similarly reduced inhibitory activity, eventually resulting in an exacerbated disease course of experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis. Therefore, by combining human and mouse analyses we show that CD226 exhibits an important role in the activation of regulatory T cells, with its genetically imposed dysregulation impairing regulatory T cell function.
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PMID:Multiple sclerosis associated genetic variants of CD226 impair regulatory T cell function. 2635 90

Treatment targeting CD226 can ameliorate experimental autoimmune encephalomyelitis (EAE), the widely accepted model of MS. However, the mechanisms still need to be elucidated. Here we showed that CD226 blockage by anti-CD226 blocking mAb LeoA1 efficiently promoted IL-10 production in human peripheral blood monocytes (PBMC) or in mixed lymphocyte culture (MLC) system, significantly induced the CD4+IL-10+ T cell differentiation while suppressing the generation of Th1 and Th17. Furthermore, CD226 pAb administration in vivo reduced the onset of EAE in mice by promoting IL-10 production and regulating T cell differentiation. Concomitantly, the onset and severity of EAE were reduced and the serum IL-10 expression levels were increased in CD226 knockout mice than that in control mice when both received EAE induction. These novel findings confirmed that CD226 played a pivotal role in mediating autoimmune diseases such as EAE. Furthermore, to our knowledge, we show for the first time that IL-10 is an important contributor in the inhibitory effects of CD226 ligation on EAE.
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PMID:CD226 ligation protects against EAE by promoting IL-10 expression via regulation of CD4+ T cell differentiation. 2694 85

The Cluster of differentiation 226(CD226)/T cell immunoglobulin and immune receptor tyrosine-based inhibitory motif domain (TIGIT) axis plays an important role in the balance of the immune response. A previous study showed that CD226 is involved in CD4+ T cell differentiation and that blocking CD226 may attenuate experimental autoimmune encephalomyelitis (EAE) development. However, the molecular mechanisms underlying this process remain incompletely understood. In this study, it was found that Cd226-/- mice were less susceptible to EAE and that there was less T helper 17(Th17) cell infiltration with higher levels of regulatory cells (Tregs) infiltration in the Cd226-/- EAE mouse central nervous system (CNS) compared with that in the WT EAE mouse CNS. Moreover, the suppressive function of Cd226-/- Tregs was upregulated compared with that of WT Tregs. Furthermore, it was observed that the expression levels of CTLA-4 and TIGIT on Cd226-/- Tregs were higher than those on WT Tregs during EAE in the spleen and CNS. Our results demonstrate a pivotal role for CD226 in attenuating Treg function in EAE that was associated with downregulating the expression levels of CTLA-4 and TIGIT.
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PMID:CD226 attenuates Treg suppressive capacity via CTLA-4 and TIGIT during EAE. 3191 90