Protein tyrosine phosphatase PTPN22 regulates IL-1β dependent Th17 responses by modulating dectin-1 signaling in mice.
Protein tyrosine phosphatase PTPN22 regulates IL-1β dependent Th17 responses by modulating dectin-1 signaling in mice.
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DOI：
10.1002/eji.201747092
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发表时间：
2018-03
影响因子：
5.4
通讯作者：
Cope AP
中科院分区：
文献类型：
--
作者：
Purvis HA;Clarke F;Jordan CK;Blanco CS;Cornish GH;Dai X;Rawlings DJ;Zamoyska R;Cope AP
A single nucleotide polymorphism within the PTPN22 gene is a strong genetic risk factor predisposing to the development of multiple autoimmune diseases. PTPN22 regulates Syk and Src family kinases downstream of immuno‐receptors. Fungal β‐glucan receptor dectin‐1 signals via Syk, and dectin‐1 stimulation induces arthritis in mouse models. We investigated whether PTPN22 regulates dectin‐1 dependent immune responses. Bone marrow derived dendritic cells (BMDCs) generated from C57BL/6 wild type (WT) and Ptpn22−/− mutant mice, were pulsed with OVA323‐339 and the dectin‐1 agonist curdlan and co‐cultured in vitro with OT‐II T‐cells or adoptively transferred into OT‐II mice, and T‐cell responses were determined by immunoassay. Dectin‐1 activated Ptpn22−/− BMDCs enhanced T‐cell secretion of IL‐17 in vitro and in vivo in an IL‐1β dependent manner. Immunoblotting revealed that compared to WT, dectin‐1 activated Ptpn22−/− BMDCs displayed enhanced Syk and Erk phosphorylation. Dectin‐1 activation of BMDCs expressing Ptpn22R619W (the mouse orthologue of human PTPN22R620W) also resulted in increased IL‐1β secretion and T‐cell dependent IL‐17 responses, indicating that in the context of dectin‐1 Ptpn22R619W operates as a loss‐of‐function variant. These findings highlight PTPN22 as a novel regulator of dectin‐1 signals, providing a link between genetically conferred perturbations of innate receptor signaling and the risk of autoimmune disease.
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影响因子：
--
作者：
Ruutu, Merja;Thomas, Gethin;Thomas, Ranjeny
通讯作者：
Thomas, Ranjeny
影响因子：
5.4
作者：
Osorio, Fabiola;LeibundGut-Landmann, Salome;Lochner, Matthias;Lahl, Katharina;Sparwasser, Tim;Eberl, Gerard;Reis e Sousa, Caetano
通讯作者：
Reis e Sousa, Caetano
影响因子：
4.4
作者：
Chang, Hui-Hsin;Miaw, Shi-Chuen;Ho, I-Cheng
通讯作者：
Ho, I-Cheng
影响因子：
4.8
作者：
Favata, MF;Horiuchi, KY;Trzaskos, JM
通讯作者：
Trzaskos, JM
DOI：
10.1084/jem.20132349
发表时间：
2014-10-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jia XM;Tang B;Zhu LL;Liu YH;Zhao XQ;Gorjestani S;Hsu YM;Yang L;Guan JH;Xu GT;Lin X
通讯作者：
Lin X