Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel.
Nat Commun. 2021 Mar 25;12(1):1893. doi: 10.1038/s41467-021-22230-z.
B cells have essential functions in multiple sclerosis and in its mouse model, experimental autoimmune encephalomyelitis, both as drivers and suppressors of the disease. The suppressive effects are driven by a regulatory B cell (Breg) population that functions, primarily but not exclusively, via the production of IL-10. However, the mechanisms modulating IL-10-producing Breg abundance are poorly understood. Here we identify SLAMF5 for controlling IL-10 Breg maintenance and function. In EAE, the deficiency of SLAMF5 in B cells causes accumulation of IL10 Bregs in the central nervous system and periphery. Blocking SLAMF5 in vitro induces both human and mouse IL-10-producing Breg cells and increases their survival with a concomitant increase of a transcription factor, c-Maf. Finally, in vivo SLAMF5 blocking in EAE elevates IL-10 Breg levels and ameliorates disease severity. Our results suggest that SLAMF5 is a negative moderator of IL-10 Breg cells, and may serve as a therapeutic target in MS and other autoimmune diseases.
B 细胞在多发性硬化症及其小鼠模型实验性自身免疫性脑脊髓炎中具有重要功能，既是疾病的驱动因素也是抑制因素。抑制作用是由调节性 B 细胞（Breg）群驱动的，主要但并非唯一通过产生 IL-10 发挥作用。然而，调节产生 IL-10 的 Breg 丰度的机制尚不清楚。在这里，我们确定 SLAMF5 可控制 IL-10 Breg 的维持和功能。在 EAE 中，B 细胞中 SLAMF5 的缺乏导致 IL10 Breg 在中枢神经系统和外周组织中的积累。体外阻断 SLAMF5 会诱导人和小鼠产生 IL-10 的 Breg 细胞，并增加其存活率，同时增加转录因子 c-Maf。最后，体内阻断 SLAMF5 在 EAE 中可提高 IL-10 Breg 水平并改善疾病严重程度。我们的结果表明，SLAMF5 是 IL-10 Breg 细胞的负调节剂，可能成为 MS 和其他自身免疫性疾病的治疗靶点。
