Department of Rheumatology and Autoimmunology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China.
School of Clinical and Basic Medicine, Shandong First Medical University &Shandong Academy of Medical Sciences, Jinan, China.
Immunology. 2023 Sep;170(1):134-153. doi: 10.1111/imm.13654. Epub 2023 May 3.
Soluble CD83 (sCD83) exerts immunosuppressive functions in many autoimmune diseases, including experimental autoimmune uveitis (EAU), but the cells and mechanisms involved are unclear. This study showed that CD83 B cells were the main sources of sCD83. They alleviated the symptoms of EAU and decreased the percentage of T cells and DCs in the eyes and lymph nodes. These CD83 B cells decreased IL-1β, IL-18 and IFN-γ secretion by DCs through sCD83. sCD83 interacted with GTPase Ras-related protein (Rab1a) in DCs to promote Rab1a accumulation in autolysosomes and inhibit mTORC1 phosphorylation and NLRP3 expression. Hence, CD83 B cells play a regulatory role in EAU by secreting sCD83. The lack of regulation of CD83 B cells might be an important factor leading to hyperimmune activation in patients with autoimmune uveitis. CD83 B cells suppress activated DCs in uveitis, indicating the potential therapeutic role of CD83 B cells in uveitis.
可溶性 CD83（sCD83）在许多自身免疫性疾病中发挥免疫抑制作用，包括实验性自身免疫性葡萄膜炎（EAU），但其涉及的细胞和机制尚不清楚。本研究表明，CD83 B 细胞是 sCD83 的主要来源。它们缓解了 EAU 的症状，降低了眼睛和淋巴结中 T 细胞和 DC 的百分比。这些 CD83 B 细胞通过 sCD83 降低了 DC 中 IL-1β、IL-18 和 IFN-γ 的分泌。sCD83 在 DC 中与 GTPase Ras-related protein（Rab1a）相互作用，促进 Rab1a 在自噬溶酶体中的积累，抑制 mTORC1 磷酸化和 NLRP3 表达。因此，CD83 B 细胞通过分泌 sCD83 在 EAU 中发挥调节作用。CD83 B 细胞调节缺失可能是导致自身免疫性葡萄膜炎患者过度免疫激活的一个重要因素。CD83 B 细胞抑制葡萄膜炎中的活化 DC，表明 CD83 B 细胞在葡萄膜炎中有潜在的治疗作用。
