A Self-Developed IL-6Rα Nanobody Alleviates Experimental Autoimmune Uveitis by Inhibiting Th1 and Th17 Cells.

Interleukin-6, a pleiotropic cytokine, initiates downstream signaling by binding to interleukin-6 receptor α (IL-6Rα) and glycoprotein 130 (GP130). Autoimmune uveitis, the most prevalent form of non-infectious uveitis, represents a serious sight-threatening ocular disorder. While corticosteroids remain the mainstay of treatment in clinical practice, their therapeutic utility is constrained by significant adverse effects. Emerging evidence highlights the pivotal role of IL-6 in autoimmune uveitis pathogenesis, particularly in promoting CD4+T cells differentiation into Type 17 helper T cells (Th17). In this study, we evaluated the therapeutic efficacy of a novel anti-IL-6Rα nanobody in experimental autoimmune uveitis (EAU) models. Peripheral blood mononuclear cells (PBMCs) from Vogt-Koyanagi-Harada (VKH) patients were used to further assess the translational relevance of the anti-IL-6Rα nanobody. Our results demonstrate that this nanobody not only suppressed Type 17 helper T cells but also Type 1 helper T cells (Th1). Furthermore, treatment with anti-IL-6Rα nanobody significantly reduced inflammatory mediators and ameliorated disease severity in murine models. In vitro studies using PBMCs from VKH patients revealed that the anti-IL-6Rα nanobody effectively suppressed both interferon-γ (IFN-γ) and IL-17 production. These findings collectively suggest that anti-IL-6Rα nanobody represents a promising therapeutic strategy for autoimmune uveitis.