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)

DRAK2 is a member of the death-associated protein (DAP)-like family of serine/threonine kinases. Members of this family induce apoptosis in various cell types. DRAK2, in particular, is specifically expressed in T cells and B cells, and it is differentially regulated during T cell development. To determine whether DRAK2 regulates lymphocyte apoptosis, we produced Drak2(-/-) mice. Contrary to our expectations, Drak2(-/-) T cells did not demonstrate any defects in apoptosis or negative selection; however, T cells from Drak2(-/-) mice exhibited enhanced sensitivity to T cell receptor-mediated stimulation with a reduced requirement for costimulation. These results provide evidence that DRAK2 raises the threshold for T cell activation by negatively regulating signals through the TCR. In contrast to other models of T cell hypersensitivity, Drak2(-/-) mice were remarkably resistant to experimental autoimmune encephalomyelitis (EAE). These results expose a new pathway regulating T cell activation and highlight the intricacies of induced autoimmune disease.
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PMID:A deficiency in Drak2 results in a T cell hypersensitivity and an unexpected resistance to autoimmunity. 1558 67

The signaling events involved in T cell trafficking into the central nervous system (CNS) following viral infection are not fully understood. Intracerebral infection of mice with mouse hepatitis virus (MHV) results in an acute encephalomyelitis followed by an immune-mediated demyelinating disease. Although chemokine signaling is critical in promoting T cell infiltration into the CNS and control of viral replication, additional signaling pathways have not been completely explored. DRAK2, a lymphoid-restricted serine/threonine kinase, prevents spurious T cell activation. Yet Drak2- / - mice are resistant to MOG-induced experimental autoimmune encephalomyelitis (EAE), suggesting that DRAK2 may influence T cell trafficking into the CNS. In order to further characterize the molecular mechanisms governing T cell activation and accumulation within the CNS in response to viral infection, MHV was instilled into the CNS of Drak2- / - mice. Drak2-deficient T cells possessed no obvious defects in trafficking into the CNS following MHV infection. Moreover, Drak2-deficient T cell activation, expansion and cytokine production were unimpaired in response to acute MHV infection. These results demonstrate that DRAK2 signaling is dispensable for T cell recruitment into the CNS following viral infection, suggesting that the resistance of Drak2- / - mice to EAE is not due to overt T cell trafficking defects.
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PMID:Anti-viral effector T cell responses and trafficking are not dependent upon DRAK2 signaling following viral infection of the central nervous system. 1736 98