Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee, United States of America.
PLoS One. 2019 Jul 10;14(7):e0215883. doi: 10.1371/journal.pone.0215883. eCollection 2019.
Innate CD8αα+ cells, also referred to as iCD8α cells, are TCR-negative intraepithelial lymphocytes (IEL) possessing cytokine and chemokine profiles and functions related to innate immune cells. iCD8α cells constitute an important source of osteopontin in the intestinal epithelium. Osteopontin is a pleiotropic cytokine with diverse roles in bone and tissue remodeling, but also has relevant functions in the homeostasis of immune cells. In this report, we present evidence for the role of iCD8α cells in the homeostasis of TCR-negative NKp46+NK1.1+ IEL (ILC1-like). We also show that the effect of iCD8α cells on ILC1-like IEL is enhanced in vitro by osteopontin. We show that in the absence of iCD8α cells, the number of NKp46+NK1.1+ IEL is significantly reduced. These ILC1-like cells are involved in intestinal pathogenesis in the anti-CD40 mouse model of intestinal inflammation. Reduced iCD8α cell numbers results in a milder form of intestinal inflammation in this disease model, whereas treatment with osteopontin increases disease severity. Collectively, our results suggest that iCD8α cells promote survival of NKp46+NK1.1+ IEL, which significantly impacts the development of intestinal inflammation.
固有 CD8αα+ 细胞，也称为 iCD8α 细胞，是 TCR 阴性上皮内淋巴细胞 (IEL)，具有与先天免疫细胞相关的细胞因子和趋化因子特征和功能。iCD8α 细胞构成肠道上皮中骨桥蛋白的重要来源。骨桥蛋白是一种具有多种作用的多效细胞因子，在骨骼和组织重塑中具有重要作用，但在免疫细胞的稳态中也具有相关功能。在本报告中，我们提供了证据表明 iCD8α 细胞在 TCR 阴性 NKp46+NK1.1+ IEL（ILC1 样）的稳态中起作用。我们还表明，骨桥蛋白在体外增强了 iCD8α 细胞对 ILC1 样 IEL 的作用。我们表明，在没有 iCD8α 细胞的情况下，NKp46+NK1.1+ IEL 的数量显著减少。这些 ILC1 样细胞参与抗 CD40 小鼠模型中的肠道炎症的肠道发病机制。在这种疾病模型中，减少 iCD8α 细胞数量会导致更温和的肠道炎症形式，而骨桥蛋白的治疗会增加疾病的严重程度。总之，我们的结果表明，iCD8α 细胞促进 NKp46+NK1.1+ IEL 的存活，这对肠道炎症的发展有重大影响。
