Subbarayal Brinda, Chauhan Sunil K, Di Zazzo Antonio, Dana Reza
Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114.
Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114
J Immunol. 2016 Nov 1;197(9):3464-3470. doi: 10.4049/jimmunol.1502641. Epub 2016 Sep 21.
Accumulating evidence shows that IL-17 is critically involved in diverse autoimmune diseases. However, its effect on the induction and progression of the humoral immune response is not fully understood. Using a preclinical model of IL-17-mediated dry eye disease, we demonstrate that upon encountering both the BCR and a secondary T cell signal, IL-17 can enhance B cell proliferation and germinal center formation in dry eye disease mice, suggesting that a stable Ag-dependent T-B cell interaction is required. Additionally, IL-17 also promotes the differentiation of B cells into isotype-switched B cells and plasma cells. Furthermore, we show that Th17 cells are more effective than Th1 cells to provide B cell help. Reduced B cell response correlates with significant reduction in clinical disease after in vivo IL-17A neutralization. In conclusion, our findings demonstrate a new role of IL-17 in promoting autoimmunity in part through directly enhancing B cell proliferation, differentiation, and plasma cell generation.
越来越多的证据表明，白细胞介素-17（IL-17）与多种自身免疫性疾病密切相关。然而，其对体液免疫反应的诱导和进展的影响尚未完全明确。利用IL-17介导的干眼病临床前模型，我们证明，在同时遇到B细胞受体（BCR）和次级T细胞信号时，IL-17可增强干眼病小鼠的B细胞增殖和生发中心形成，这表明需要稳定的抗原依赖性T-B细胞相互作用。此外，IL-17还促进B细胞分化为同种型转换的B细胞和浆细胞。此外，我们发现辅助性T细胞17（Th17）细胞比辅助性T细胞1（Th1）细胞更有效地为B细胞提供帮助。体内IL-17A中和后，B细胞反应降低与临床疾病显著减轻相关。总之，我们的研究结果表明，IL-17在部分通过直接增强B细胞增殖、分化和浆细胞生成来促进自身免疫方面具有新作用。
