SHP-2 Mediates C-type Lectin Receptors-induced Syk Activation and Anti-fungal T(H)17 Responses

Fungal infection stimulates the canonical C-type lectin receptors (CLRs) signaling pathway via Syk activation. Here we show that SHP-2 plays a crucial role in mediating CLRs-induced Syk activation. Genetic ablation of Shp-2 (Ptpn11) in dendritic cells (DCs) and macrophages impaired Syk-mediated sign...

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Detalles Bibliográficos
Autores principales: Deng, Zihou, Ma, Shixin, Zhou, Hao, Zang, Aiping, Fang, Yiyuan, Li, Tiantian, Shi, Huanjing, Liu, Mei, Du, Min, Taylor, Patricia R., Zhu, Helen H., Chen, Jiangye, Meng, Guangxun, Li, Fubin, Chen, Changbin, Zhang, Yan, Jia, Xin-Ming, Lin, Xin, Zhang, Xiaoming, Pearlman, Eric, Li, Xiaoxia, Feng, Gen-Sheng, Xiao, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439382/
https://www.ncbi.nlm.nih.gov/pubmed/25915733
http://dx.doi.org/10.1038/ni.3155
Descripción
Sumario:Fungal infection stimulates the canonical C-type lectin receptors (CLRs) signaling pathway via Syk activation. Here we show that SHP-2 plays a crucial role in mediating CLRs-induced Syk activation. Genetic ablation of Shp-2 (Ptpn11) in dendritic cells (DCs) and macrophages impaired Syk-mediated signaling and abrogated pro-inflammatory gene expression following fungal stimulation. Mechanistically, SHP-2 operates as a scaffold facilitating the recruitment of Syk to dectin-1 or FcRγ, through its N-SH2 domain and a previously unrecognized C-terminal ITAM motif. We demonstrate that DC-derived SHP-2 is crucial for the induction of IL-1β, IL-6 and IL-23, and anti-fungal T(H)17 cell responses to control Candida albicans infection. Together, these data reveal a mechanism by which SHP-2 mediates Syk activation in response to fungal infections

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