دورية
Myeloid Src-family kinases are critical for neutrophil-mediated autoinflammation in gout and motheaten models
| العنوان: | Myeloid Src-family kinases are critical for neutrophil-mediated autoinflammation in gout and motheaten models |
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| المؤلفون: | Futosi, Krisztina, Németh, Tamás, Horváth, Ádám I., Abram, Clare L., Tusnády, Simon, Lowell, Clifford A., Helyes, Zsuzsanna, Mócsai, Attila |
| المصدر: | The Journal of Experimental Medicine; July 2023, Vol. 220 Issue: 7 pe20221010-e20221010, 1p |
| مستخلص: | Autoinflammatory diseases include a number of monogenic systemic inflammatory diseases, as well as acquired autoinflammatory diseases such as gout. Here, we show that the myeloid Src-family kinases Hck, Fgr, and Lyn are critical for experimental models of gout, as well as for genetically determined systemic inflammation in the Ptpn6me-v/me-v (motheaten viable) mouse model. The Hck−/−Fgr−/−Lyn−/− mutation abrogated various monosodium urate (MSU) crystal–induced pro-inflammatory responses of neutrophils, and protected mice from the development of gouty arthritis. The Src-family inhibitor dasatinib abrogated MSU crystal–induced responses of human neutrophils and reduced experimental gouty arthritis in mice. The Hck−/−Fgr−/−Lyn−/− mutation also abrogated spontaneous inflammation and prolonged the survival of the Ptpn6me-v/me-v mice. Spontaneous adhesion and superoxide release of Ptpn6me-v/me-v neutrophils were also abolished by the Hck−/−Fgr−/−Lyn−/− mutation. Excessive activation of tyrosine phosphorylation pathways in myeloid cells may characterize a subset of autoinflammatory diseases. |
| قاعدة البيانات: | Supplemental Index |
Full Text Finder | تدمد: | 00221007 15409538 |
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| DOI: | 10.1084/jem.20221010 |