The adaptor protein Rai/ShcC promotes astrocyte-dependent inflammation during experimental autoimmune encephalomyelitis

Cristina Ulivieri, Maria Teresa Savino, Ilaria Luccarini, Emanuela Fanigliulo, Alessandra Aldinucci, Elena Bonechi, Marisa Benagiano, Barbara Ortensi, Giuliana Pelicci, Mario Milco D'Elios, Clara Ballerini, Cosima Tatiana Baldari

Research output: Contribution to journalArticle

Abstract

Th17 cells have been casually associated to the pathogenesis of autoimmune disease. We have previously demonstrated that Rai/ ShcC, a member of the Shc family of adaptor proteins, negatively regulates Th17 cell differentiation and lupus autoimmunity. In this study, we have investigated the pathogenic outcome of the Th17 bias associated with Rai deficiency on multiple sclerosis development, using the experimental autoimmune encephalomyelitis (EAE) mouse model.We found that, unexpectedly, EAE was less severe in Rai2/2 mice compared with their wild-type counterparts despite an enhanced generation of myelin-specific Th17 cells that infiltrated into the CNS. Nevertheless, when adoptively transferred into immunodeficient Rai+/+ mice, these cells promoted a more severe disease compared with wild-type encephalitogenic Th17 cells. This paradoxical phenotype was caused by a dampened inflammatory response of astrocytes, which were found to express Rai, to IL-17. The results provide evidence that Rai plays opposite roles in Th17 cell differentiation and astrocyte activation, with the latter dominant over the former in EAE, highlighting this adaptor as a potential novel target for the therapy of multiple sclerosis.

Original languageEnglish
Pages (from-to)480-490
Number of pages11
JournalJournal of Immunology
Volume197
Issue number2
DOIs
Publication statusPublished - Jul 15 2016

ASJC Scopus subject areas

  • Immunology

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    Ulivieri, C., Savino, M. T., Luccarini, I., Fanigliulo, E., Aldinucci, A., Bonechi, E., Benagiano, M., Ortensi, B., Pelicci, G., D'Elios, M. M., Ballerini, C., & Baldari, C. T. (2016). The adaptor protein Rai/ShcC promotes astrocyte-dependent inflammation during experimental autoimmune encephalomyelitis. Journal of Immunology, 197(2), 480-490. https://doi.org/10.4049/jimmunol.1502063