Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Department of Gastroenterology, Third Xiangya Hospital of Central South University, Changsha, China.
Front Immunol. 2021 Jan 6;11:579615. doi: 10.3389/fimmu.2020.579615. eCollection 2020.
Human pathogen is a significant risk factor for the development of long-term intestinal dysfunction although the cellular and molecular mechanisms remain scantily defined. IL-23 is an emerging therapeutic target for the treatment of inflammatory intestinal diseases, however its role in -driven intestinal pathology is not fully understood. IL-10 deficient mice represent a robust model to study the pathogenesis of infection because infection of mice lacking IL-10 results in symptoms and pathology that resemble human campylobacteriosis. To determine the role of IL-23 in -driven intestinal inflammation, we studied the disease pathogenesis in IL-23 mice with inhibited IL-10Rα signaling. These mice exhibited reduced intestinal pathology independent from bacterial clearance. Further, levels of IFNγ, IL-17, IL-22, TNF, and IL-6 were reduced and associated with reduced accumulation of neutrophils, monocytes and macrophages in the colon. Flow cytometry analysis revealed reduced production of IL-17 and IFNγ by group 1 and 3 innate lymphoid cells. Thus, our data suggest that IL-23 contributes to intestinal inflammation in infected mice by promoting IL-17 and IFNγ production by innate lymphoid cells.
人类病原体是导致长期肠道功能障碍的重要危险因素，尽管其细胞和分子机制仍知之甚少。IL-23 是治疗炎症性肠道疾病的新兴治疗靶点，但其在 - 驱动的肠道病理学中的作用尚未完全阐明。IL-10 缺陷型小鼠是研究 感染发病机制的强大模型，因为缺乏 IL-10 的小鼠感染会导致类似于人类弯曲杆菌病的症状和病理学。为了确定 IL-23 在 - 驱动的肠道炎症中的作用，我们研究了抑制 IL-10Rα 信号的 IL-23 小鼠中的疾病发病机制。这些小鼠表现出独立于细菌清除的肠道病理学减轻。此外，IFNγ、IL-17、IL-22、TNF 和 IL-6 的水平降低，与结肠中中性粒细胞、单核细胞和巨噬细胞的积累减少相关。流式细胞术分析显示，I 型和 III 型固有淋巴细胞产生的 IL-17 和 IFNγ 减少。因此，我们的数据表明，IL-23 通过促进固有淋巴细胞产生 IL-17 和 IFNγ 来促进 感染小鼠的肠道炎症。
