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

被引：10

作者：

Savino, Maria Teresa ^{[1
]}

Ulivieri, Cristina ^{[1
]}

Emmi, Giacomo ^{[3
]}

Prisco, Domenico ^{[3
]}

De Falco, Giulia ^{[2
]}

Ortensi, Barbara ^{[5
]}

Beccastrini, Enrico ^{[4
]}

Emmi, Lorenzo ^{[4
]}

Pelicci, Giuliana ^{[5
]}

D'Elios, Mario M. ^{[6
]}

Baldari, Cosima T. ^{[1
]}

机构：

[1] Univ Siena, Dept Life Sci, I-53100 Siena, Italy

[2] Univ Siena, Dept Anat Pathol, I-53100 Siena, Italy

[3] Azienda Osped Univ Careggi, Dept Med Pathol, Policlin Careggi, Florence, Italy

[4] Azienda Osped Univ Careggi, Lupus Clin, Policlin Careggi, Florence, Italy

[5] European Inst Oncol, Dept Expt Oncol, Milan, Italy

[6] Univ Florence, Dept Internal Med, Florence, Italy

来源：

JOURNAL OF LEUKOCYTE BIOLOGY | 2013年 / 93卷 / 04期

关键词：

Th2; cells; T cell receptors; cell differentiation; signal transduction; systemic lupus erythematosus; SYSTEMIC-LUPUS-ERYTHEMATOSUS; T-CELLS; CUTTING EDGE; IFN-GAMMA; ACTIVATION; AUTOIMMUNITY; EFFECTOR; EXPRESSION; SUBSETS; IL-17;

D O I：

10.1189/jlb.0712331

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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. J. Leukoc. Biol. 93: 549-559; 2013.

引用

页码：549 / 559

页数：11

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[1] Translational Mini-Review Series on Th17 Cells: Induction of interleukin-17 production by regulatory T cells [J].