Altered thymic selection by overexpressing cellular FLICE inhibitory protein in T cells causes lupus-like syndrome in a BALB/c but not C57BL/6 strain.
Altered thymic selection by overexpressing cellular FLICE inhibitory protein in T cells causes lupus-like syndrome in a BALB/c but not C57BL/6 strain.
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DOI：
10.1038/cdd.2009.143
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发表时间：
2010-03
影响因子：
12.4
通讯作者：
Zhang, J.
中科院分区：
文献类型：
--
作者：
Qiao, G.;Li, Z.;Minto, A. W.;Shia, J.;Yang, L.;Bao, L.;Tschopp, J.;Gao, J-X;Wang, J.;Quigg, R. J.;Zhang, J.
Cellular FLICE inhibitory protein (c-FLIP) is an endogenous inhibitor of the caspase-8 pro-apoptotic signaling pathway downstream of death receptors. Recent evidence indicates that the long form of c-FLIP (c-FLIPL) is required for proliferation and effector T cell development. However, the role of c-FLIPL in triggering autoimmunity has not been carefully investigated. We now report that c-FLIPL transgenic (Tg) mice develop splenomegaly, lymphadenopathy, multi-organ infiltration, high titers of autoantibodies, and proliferative glomerulonephritis with immune complex deposition in a strain-dependent fashion. The development of autoimmunity requires CD4+ T cells and may result from impaired thymic selection. At the molecular level, c-FLIPL over-expression inhibits the ZAP-70 activation, thus impairing the signaling pathway derived from ZAP-70 required for thymic selection. Therefore, we have identified c-FLIPL as a susceptibility factor under the influence of epistatic modifiers for the development of autoimmunity.
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