PSTPIP2 inhibits neutrophil extracellular trap formation through its interaction with PTPN22 2216
Year: 2025
Type: article
Abstract: Description Neutrophils are highly inflammatory cells that are the first line of defense in innate immune responses. They are the most abundant leukocyte in circulation and turnover is rapid as they are short-lived. Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2) is highly expressed by neutrophils at steady state. Known targets of PSTPIP2 include the phosphatases SHIP1, CSK, and PTP-PEST. However, it is unclear whether these interactions are activating or inhibitory, and PSTPIP2’s role in neutrophil function remains elusive. Our lab and others have found that neutrophils isolated from Pstpip2cmo mice, that are deficient in PSTPIP2, display a hyperinflammatory phenotype with increased secretion of IL-1β and ROS following stimulation compared to wild-type (WT) mice. Further, we’ve observed more neutrophil extracellular traps (NETs) in response to Pseudomonas aeruginosa in Pstpip2cmo neutrophils. To dissect the mechanism leading to enhanced NETosis, we examined the phosphatase protein tyrosine phosphatase non-receptor 22 (PTPN22) which is predicted to interact with PSTPIP2. Co-immunoprecipitation of PTPN22 showed that PSTPIP2 indeed interacts with PTPN22 at steady state. Moreover, PTPN22 also interacts with protein arginine deiminase 4 (PAD4) upon P. aeruginosa stimulation. Specific inhibition of PTPN22 results in decreased NETosis and citrullinated histone H3 suggesting that PSTPIP2 inhibits PTPN22 from activating PAD4 suppressing histone citrullination and NETosis. Funding Sources Supported by 1T32HL170963-01A1 Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)
Source: The Journal of Immunology
Authors: Bridget Ratitong, Claire Momjian, Sheryl Fernandes, Peter Allan Jorth, Suzanne Cassel, Fayyaz S Sutterwala
Institution: Cedars-Sinai Medical Center
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416449233
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