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 Rai(-/-) 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

The adaptor protein Rai/ShcC promotes astrocyte-dependent inflammation during Experimental Autoimmune Encephalomyelitis / Ulivieri, C; Savino, M; Luccarini, I; Fanigliulo, E; Aldinucci, A; Bonechi, E; Benagiano, M; Ortensi, B; Pelicci, G; D'Elios, Mm; Ballerini, C; Baldari, Ct.. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - ELETTRONICO. - 197:(2016), pp. 480-490. [10.4049/jimmunol.1502063]

The adaptor protein Rai/ShcC promotes astrocyte-dependent inflammation during Experimental Autoimmune Encephalomyelitis.

LUCCARINI, ILARIA;BONECHI, ELENA;BENAGIANO, MARISA;D'ELIOS, MARIO MILCO;BALLERINI, CLARA;
2016

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 Rai(-/-) 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
197
480
490
Ulivieri, C; Savino, M; Luccarini, I; Fanigliulo, E; Aldinucci, A; Bonechi, E; Benagiano, M; Ortensi, B; Pelicci, G; D'Elios, Mm; Ballerini, C; Baldari, Ct.
File in questo prodotto:
File Dimensione Formato  
JImm 2016.pdf

Accesso chiuso

Tipologia: Pdf editoriale (Version of record)
Licenza: DRM non definito
Dimensione 1.68 MB
Formato Adobe PDF
1.68 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1055172
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 6
social impact