Aggregation of Fc epsilon RI on mast cells activates signaling pathways, resulting in degranulation and cytokine release. Release of mast cell-derived inflammatory mediators is tightly regulated by the interplay of positive and negative signals largely orchestrated by adapter proteins. Among these, the Shc family adapter p52Shc, which couples immunoreceptors to Ras activation, positively regulates Fc epsilon RI-dependent signaling. Conversely, p66Shc was shown to uncouple the TCR for the Ras-MAPK pathway and prime T cells to undergo apoptotic death. Loss of p66Shc in mice results in breaking of immunologic tolerance and development of lupus-like autoimmune disease, which includes alopecia among its pathological manifestations. The presence of numerous activated mast cells in alopecic skin areas suggests a role for this adapter in mast cells. In this study, we addressed the involvement of p66Shc in Fc epsilon RI-dependent mast cell activation. We showed that p66Shc is expressed in mast cells and that mast cells from p66Shc(-/-) mice exhibit enhanced responses following Ag stimulation of Fc epsilon RI. Furthermore, using RBL-2H3 cell transfectants, we showed that aggregation of Fc epsilon RI resulted in the recruitment of a p66Shc-SHIP1 complex to linker for activation of T cells. Collectively, our data identified p66Shc as a negative regulator of mast cell activation.

Ulivieri, C., Fanigliulo, D., Masi, G., Savino, M.T., Gamberucci, A., Pelicci, P.g., et al. (2011). p66Shc is a negative regulator of FcεRI-dependent signalling in mast cells. JOURNAL OF IMMUNOLOGY, 186(9), 5095-5106 [10.4049/jimmunol.1001391].

p66Shc is a negative regulator of FcεRI-dependent signalling in mast cells

ULIVIERI, CRISTINA;FANIGLIULO, DANIELA;MASI, GIULIA;SAVINO, MARIA TERESA;GAMBERUCCI, ALESSANDRA;BALDARI, COSIMA
2011-01-01

Abstract

Aggregation of Fc epsilon RI on mast cells activates signaling pathways, resulting in degranulation and cytokine release. Release of mast cell-derived inflammatory mediators is tightly regulated by the interplay of positive and negative signals largely orchestrated by adapter proteins. Among these, the Shc family adapter p52Shc, which couples immunoreceptors to Ras activation, positively regulates Fc epsilon RI-dependent signaling. Conversely, p66Shc was shown to uncouple the TCR for the Ras-MAPK pathway and prime T cells to undergo apoptotic death. Loss of p66Shc in mice results in breaking of immunologic tolerance and development of lupus-like autoimmune disease, which includes alopecia among its pathological manifestations. The presence of numerous activated mast cells in alopecic skin areas suggests a role for this adapter in mast cells. In this study, we addressed the involvement of p66Shc in Fc epsilon RI-dependent mast cell activation. We showed that p66Shc is expressed in mast cells and that mast cells from p66Shc(-/-) mice exhibit enhanced responses following Ag stimulation of Fc epsilon RI. Furthermore, using RBL-2H3 cell transfectants, we showed that aggregation of Fc epsilon RI resulted in the recruitment of a p66Shc-SHIP1 complex to linker for activation of T cells. Collectively, our data identified p66Shc as a negative regulator of mast cell activation.
Ulivieri, C., Fanigliulo, D., Masi, G., Savino, M.T., Gamberucci, A., Pelicci, P.g., et al. (2011). p66Shc is a negative regulator of FcεRI-dependent signalling in mast cells. JOURNAL OF IMMUNOLOGY, 186(9), 5095-5106 [10.4049/jimmunol.1001391].
File in questo prodotto:
File Dimensione Formato  
Ulivieri et al J Immunol 2011.pdf

non disponibili

Tipologia: Post-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 1.54 MB
Formato Adobe PDF
1.54 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS 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/11365/20213
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo