The dual-specificity phosphatase JSP1 regulates neutrophil adhesion via integrin-SRC signaling in vascular inflammation

Li, Li, Tonks, Nicholas K (March 2026) The dual-specificity phosphatase JSP1 regulates neutrophil adhesion via integrin-SRC signaling in vascular inflammation. Journal of Biological Chemistry, 302 (5). p. 111369. ISSN 0021-9258

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URL: https://www.ncbi.nlm.nih.gov/pubmed/41850398

DOI: 10.1016/j.jbc.2026.111369

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-TNF-alpha-induced vascular injury. JSP1-knockout 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-knockout neutrophils is consistent with a mechanism involving impaired integrin-SRC signaling. These findings establish JSP1 as a key regulator of neutrophil-driven vascular inflammation.

Item Type:	Paper
Subjects:	diseases & disorders organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions diseases & disorders > inflammation organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neutrophils organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neutrophils organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neutrophils organs, tissues, organelles, cell types and functions
CSHL Authors:	Tonks, Nicholas K. Li, Li
Communities:	CSHL labs > Tonks lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	16 March 2026
Date Deposited:	20 Apr 2026 13:06
Last Modified:	20 Apr 2026 13:06
PMCID:	PMC13090511
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/42161

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