Rai, a Shc adapter family member, acts as a negative regulator of antigen receptor signaling in T and B cells. Rai(-/-) mice develop lupus-like autoimmunity associated to the spontaneous activation of self-reactive lymphocytes. Here, we have addressed the potential role of Rai in the development of the proinflammatory Th1 and Th17 subsets, which are centrally implicated in the pathogenesis of a number of autoimmune diseases, including lupus. We show that Rai(-/-) mice display a spontaneous Th1/Th17 bias. In vitro polarization experiments on naive and effector/memory CD4(+) T cells demonstrate that Rai(-/-) favors the development and expansion of Th17 but not Th1 cells, indicating that Rai modulates TCR signaling to antagonize the pathways driving naive CD4(+) T cell differentiation to the Th17 lineage, while indirectly limiting Th1 cell development in vivo. Th1 and Th17 cell infiltrates were found in the kidneys of Rai(-/-) mice, providing evidence that Rai(-/-) contributes to the development of lupus nephritis, not only by enhancing lymphocyte activation but also by promoting the development and expansion of proinflammatory effector T cells. Interestingly, T cells from SLE patients were found to have a defect in Rai expression, suggesting a role for Rai in disease pathogenesis.

Savino, M.T., Ulivieri, C., G., E., D., P., DE FALCO, G., B., O., et al. (2013). The Shc family protein adaptor, Rai, acts as a negative regulator of Th17 and Th1 cell development. JOURNAL OF LEUKOCYTE BIOLOGY, 93, 549-559 [10.1189/jlb.0712331].

The Shc family protein adaptor, Rai, acts as a negative regulator of Th17 and Th1 cell development

SAVINO, MARIA TERESA;ULIVIERI, CRISTINA;DE FALCO, GIULIA;M. M. D'Elios;BALDARI, COSIMA
2013-01-01

Abstract

Rai, a Shc adapter family member, acts as a negative regulator of antigen receptor signaling in T and B cells. Rai(-/-) mice develop lupus-like autoimmunity associated to the spontaneous activation of self-reactive lymphocytes. Here, we have addressed the potential role of Rai in the development of the proinflammatory Th1 and Th17 subsets, which are centrally implicated in the pathogenesis of a number of autoimmune diseases, including lupus. We show that Rai(-/-) mice display a spontaneous Th1/Th17 bias. In vitro polarization experiments on naive and effector/memory CD4(+) T cells demonstrate that Rai(-/-) favors the development and expansion of Th17 but not Th1 cells, indicating that Rai modulates TCR signaling to antagonize the pathways driving naive CD4(+) T cell differentiation to the Th17 lineage, while indirectly limiting Th1 cell development in vivo. Th1 and Th17 cell infiltrates were found in the kidneys of Rai(-/-) mice, providing evidence that Rai(-/-) contributes to the development of lupus nephritis, not only by enhancing lymphocyte activation but also by promoting the development and expansion of proinflammatory effector T cells. Interestingly, T cells from SLE patients were found to have a defect in Rai expression, suggesting a role for Rai in disease pathogenesis.
Savino, M.T., Ulivieri, C., G., E., D., P., DE FALCO, G., B., O., et al. (2013). The Shc family protein adaptor, Rai, acts as a negative regulator of Th17 and Th1 cell development. JOURNAL OF LEUKOCYTE BIOLOGY, 93, 549-559 [10.1189/jlb.0712331].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/45830
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