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  • Title: Signal inhibitory receptor on leukocytes-1 regulates the formation of the neutrophil extracellular trap in rheumatoid arthritis.
    Author: Wang L, Yuan J, Cheng Y, Xu Z, Ding M, Li J, Si Y, Zong M, Fan L.
    Journal: Mol Immunol; 2022 Nov; 151():242-251. PubMed ID: 36182788.
    Abstract:
    BACKGROUND: Neutrophil extracellular trap (NET) has been demonstrated to play important roles in the pathogenesis and progression of rheumatoid arthritis (RA). Emerging evidence indicates that ligation of signal inhibitory receptor on leukocytes-1 (SIRL-1) can dampen Fc receptor-induced reactive oxygen species (ROS) production in primary human neutrophils by reducing extracellular signal-regulated kinase (ERK) activation. The current study aimed to determine the regulatory effects of SIRL-1 on the NET formation and ROS production by comparing RA patients and healthy controls (HC). METHODS: Multiple assays were employed to detect the expression level of SIRL-1, including immunohistochemical staining, quantitative reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry. Peripheral blood neutrophils from both HC and RA patients were freshly isolated. The NET formation was assessed spontaneously before and after exposure to serum samples from HC and RA patients, respectively. The quantification of NET formation was determined by fluorescence microscopy and Spectra Max M5 fluorescent plate reader. The ROS production was examined by flow cytometry. RESULTS: The expression level of SIRL-1 in peripheral blood neutrophils was decreased in RA, comparing to HC. The RA-originated neutrophils showed higher levels of ROS production and NET formation. Ligation of SIRL-1 to neutrophils suppressed ROS production and NET formation. Stimulation of neutrophils with severe anti-cyclic citrullinated peptides (CCP) induced NET formation, which could be inhibited by application of SIRL-1 ligation. CONCLUSION: The current study identified SIRL-1 differentially expressed in neutrophils between RA and HC. Ligation of SIRL-1 inhibited ROS production and NET formation. Downregulation of SIRL-1 showed correlation with upregulation of NET formation in RA. These findings showed the regulation of SIRL-1 on NET formation and provided a potential therapeutic target for RA.
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