Signaling Lymphocytic Activation Molecule Family-7 Alleviates Corneal Inflammation by Promoting M2 Polarization.

BACKGROUND Signaling Lymphocytic Activation Molecule Family-7 (SLAMF7) functions an immune checkpoint molecule on macrophages in anti-tumor immunity. However, its role in bacterial infection remains largely unknown. METHODS Bone marrow-derived macrophages (BMDMs) isolated from wild type (WT) or SLAMF7 knockout (KO) mice were infected with bacteria or treated with LPS/IFN-γ to investigate the expression and function of SLAMF7 in macrophage polarization. Pseudomonas aeruginosa (P. aeruginosa) keratitis murine model was established to explore the effect of SLAMF7 on P. aeruginosa keratitis, using WT vs SLAMF7 KO mice, or recombinant SLAMF7 vs PBS-treated mice, respectively. RESULTS SLAMF7 expression was enhanced on M1-polarized or bacterial-infected macrophages, and infiltrating macrophages in P. aeruginosa-infected mouse corneas. SLAMF7 promoted M2 polarization by inducing STAT6 activation. In vivo data showed that SLAMF7 KO aggravated, while treatment with recombinant SLAMF7 alleviated, corneal inflammation and disease severity. Besides, blockage of M2 polarization by Arg-1 inhibitor abrogated the effect of recombinant SLAMF7 in disease progression. CONCLUSIONS SLAMF7 expression in macrophages was induced upon M1-polarization or bacteria-infection and alleviated corneal inflammation and disease progression of P. aeruginosa keratitis via promoting M2 polarization. These findings may provide a potential strategy for the treatment of P. aeruginosa keratitis.