Myeloid Src-family kinases are critical for neutrophil-mediated autoinflammation in gout and motheaten models
| Autor: | Krisztina Futosi, Tamás Németh, Ádám I. Horváth, Clare L. Abram, Simon Tusnády, Clifford A. Lowell, Zsuzsanna Helyes, Attila Mócsai |
|---|---|
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Journal of Experimental Medicine. 220 |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|