Li, Li, Tonks, Nicholas K (September 2025) JSP1 Regulates Neutrophil Adhesion via Integrin-SRC Signaling in Vascular Inflammation. bioRxiv. ISSN 2692-8205 (Submitted)
Abstract
The c-JUN N-terminal kinase (JNK) signaling pathway plays an important role in regulating the innate immune response. Immune signaling is governed by the coordinated activity of protein kinases counter-balanced by protein phosphatases; however, the importance of the latter family of enzymes is less well understood. c-JUN N-terminal kinase (JNK)-stimulatory phosphatase 1 (JSP1, also known as DUSP22) has been implicated as a positive regulator of JNK signaling, yet its role in innate immunity is not clear. Using a mouse model of the local Shwartzman reaction, we show that JSP1 is essential for LPS-TNFα-induced vascular injury. JSP1-deficient mice exhibited reduced vascular hemorrhage. Neutrophil depletion and adoptive transfer experiments confirmed that JSP1-expressing neutrophils mediate this injury. JSP1 was not required for neutrophil development or surface receptor abundance but was essential for integrin activation and adhesion. Reduced SYK and HCK phosphorylation in JSP1-deficient neutrophils are consistent with a mechanism involving impaired integrin-SRC signaling. These findings establish JSP1 as a key regulator of neutrophil-driven vascular inflammation.
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