Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
J Immunol. 2018 Aug 15;201(4):1267-1274. doi: 10.4049/jimmunol.1800484. Epub 2018 Jul 6.
Glucocorticoids (GCs) are commonly prescribed to patients with a variety of inflammatory disorders, including inflammatory bowel disease (IBD). GCs mediate their immunomodulatory effects through many different mechanisms and target multiple signaling pathways. The GC dexamethasone downmodulates innate and adaptive immune cell activation. IBD is the manifestation of a dysregulated immune response involving many different immune cells. Group 3 innate lymphocytes (ILC3s) have critical roles in mucosal inflammation. ILC3s secrete high levels of the cytokine IL-22, promoting epithelial proliferation, antimicrobial peptides, and mucins. In this study, we examined the effects of dexamethasone on IL-22 production by ILC3s. We found that dexamethasone suppressed IL-23-mediated IL-22 production in human and mouse ILC3s. This was mediated in part through dexamethasone modulation of the NF-κB pathway. Inhibition of NF-κB signaling with a small molecule inhibitor also downmodulated IL-23- and IL-1β-mediated IL-22 production in ILC3s. These findings implicate NF-κB as a regulator of IL-22 in ILC3s and likely have repercussions on GC treatment of IBD patients.
糖皮质激素（GCs）常用于治疗各种炎症性疾病的患者，包括炎症性肠病（IBD）。GCs 通过多种不同的机制介导其免疫调节作用，并靶向多个信号通路。GC 地塞米松下调先天和适应性免疫细胞的激活。IBD 是涉及多种不同免疫细胞的失调免疫反应的表现。第三组先天淋巴细胞（ILC3s）在粘膜炎症中具有关键作用。ILC3s 分泌高水平的细胞因子 IL-22，促进上皮细胞增殖、抗菌肽和粘蛋白。在这项研究中，我们研究了地塞米松对 ILC3s 产生 IL-22 的影响。我们发现地塞米松抑制了人源和鼠源 ILC3s 中 IL-23 介导的 IL-22 产生。这部分是通过地塞米松对 NF-κB 途径的调节介导的。用小分子抑制剂抑制 NF-κB 信号也下调了 ILC3s 中 IL-23 和 IL-1β 介导的 IL-22 产生。这些发现表明 NF-κB 是 ILC3s 中 IL-22 的调节剂，可能对 GC 治疗 IBD 患者产生影响。
