TREM2通过介导巨噬细胞胞葬功能减轻大疱性类天疱疮的炎性反应OA

Objective To investigate the effect of TREM2 on the inflammatory response at le-sional sites of bullous pemphigoid(BP)by regulating macrophage efferocytosis.Methods We analyzed the expression of TREM2,the proportion and function of TREM2+MΦs using the single cell RNA-sequencing data of lesional skin tissues from BP patients(NGDC#HRA003993).Bioinformatic analysis was performed to identify differentially expressed genes(DEGs),enriched signaling pathways,and functional differences between TREM2+MΦs and TREM2-MΦs,and the correlation between TREM2 expression and inflammatory factor levels in BP skin lesions.Addition-ally,H&E and immunofluorescence staining of C3 were used to evaluate the pathological changes in the lesional skin tissues.The number of TREM2+MΦs in BP skin lesions was analyzed by im-munofluorescence staining.Finally,Bone marrow-derived macrophages(BMDMs)from(wild type,WT)and Trem2 knockout(Trem2 KO)mice were cultured in vitro.Flow cytometry was used to assess the efferocytic capacity of macrophages and to determine the effect of TREM2 ex-pression on apoptotic cell clearance.Results The lesional skin of BP patients showed typical clin-ical and pathological features of this disease.Single-cell transcriptomic analysis and immunofluo-rescence staining revealed a significant increase in the number of TREM2+MΦs in BP lesions compared to normal skin(P＜0.001),indicating a marked enrichment of this cell population in BP lesions.Furthermore,the expression levels of the inflammatory cytokines,IL-4 and IL-13,as well as the chemokines,CCL2 and CCL13,were significantly higher in BP lesional tissues and blister fluid than in normal skin(P＜0.01),and their expression levels correlated positively with TREM2 expression.For cellular phenotype,TREM2+MΦs in BP lesional tissues expressed mono-cyte markers(CD14 and FCGR3A)and M2-type macrophage markers(CD163 and MRC1),sug-gesting potential immunomodulatory functions.Functional analyses showed that TREM2+MΦs ex-hibited significant enrichment of genes associated with efferocytosis pathways and demonstrated sig-nificantly enhanced efferocytic capacity compared with TREM2-MΦs(P＜0.01).Moreover,correlation analysis indicated that TREM2 expression tended to correlate positively with IL-10(P=0.08)and negatively with IL-18(P=0.01)and IL-33(P=0.09),suggesting that TREM2-MΦs may suppress local inflammation through efferocytosis.Conclusion The increased TREM2+MΦs in BP lesional tissues may suppress inflammatory responses through efferocytosis.