Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany.
Front Immunol. 2022 Aug 1;13:970906. doi: 10.3389/fimmu.2022.970906. eCollection 2022.
IL-10 is a cytokine with pleiotropic functions, particularly known for its suppressive effects on various immune cells. Consequently, it can limit the pathogenesis of inflammatory diseases, such as multiple sclerosis (MS), inflammatory bowel disease, Crohn's disease, and Epidermolysis bullosa acquisita, among others. Recent evidence however indicates that it plays dual roles in Systemic lupus Erythematosus (SLE) where it may inhibit pro-inflammatory effector functions but seems to be also a main driver of the extrafollicular antibody response, outside of germinal centers (GC). In line, IL-10 promotes direct differentiation of activated B cells into plasma cells rather than stimulating a GC response. IL-10 is produced by B cells, myeloid cells, and certain T cell subsets, including extrafollicular T helper cells, which are phenotypically distinct from follicular helper T cells that are relevant for GC formation. In SLE patients and murine lupus models extrafollicular T helper cells have been reported to support ongoing extrafollicular formation of autoreactive plasma cells, despite the presence of GCs. Here, we discuss the role of IL-10 as driver of B cell responses, its impact on B cell proliferation, class switch, and plasma cells.
IL-10 是一种具有多种功能的细胞因子，尤其以其对各种免疫细胞的抑制作用而闻名。因此，它可以限制炎症性疾病的发病机制，如多发性硬化症 (MS)、炎症性肠病、克罗恩病和获得性大疱性表皮松解症等。然而，最近的证据表明，它在系统性红斑狼疮 (SLE) 中具有双重作用，它可能抑制促炎效应功能，但似乎也是生发中心 (GC) 外滤泡外抗体反应的主要驱动因素。同样，IL-10 促进激活的 B 细胞直接分化为浆细胞，而不是刺激 GC 反应。IL-10 由 B 细胞、髓样细胞和某些 T 细胞亚群产生，包括滤泡外辅助性 T 细胞，它们与生发中心形成相关的滤泡辅助性 T 细胞在表型上不同。在 SLE 患者和小鼠狼疮模型中，已经报道滤泡外辅助性 T 细胞尽管存在 GC，但仍支持自身反应性浆细胞的持续滤泡外形成。在这里，我们讨论了 IL-10 作为 B 细胞反应的驱动因素的作用，及其对 B 细胞增殖、类别转换和浆细胞的影响。
