Department of Pathology and Program in Molecular and Cellular Biology, University of Washington, Seattle, Washington, United States of America.
PLoS One. 2012;7(5):e37311. doi: 10.1371/journal.pone.0037311. Epub 2012 May 18.
IL-12 and IL-23 regulate innate and adaptive immunity to microbial pathogens through influencing the expression of IFN-γ, IL-17, and IL-22. Herein we define the roles of IL-12 and IL-23 in regulating host resistance and intestinal inflammation during acute Salmonella infection. We find that IL-23 alone is dispensable for protection against systemic spread of bacteria, but synergizes with IL-12 for optimal protection. IL-12 promotes the production of IFN-γ by NK cells, which is required for resistance against Salmonella and also for induction of intestinal inflammation and epithelial injury. In contrast, IL-23 controls the severity of inflammation by inhibiting IL-12A expression, reducing IFN-γ and preventing excessive mucosal injury. Our studies demonstrate that IL-23 is a homeostatic regulator of IL-12-dependent, IFN-γ-mediated intestinal inflammation.
IL-12 和 IL-23 通过影响 IFN-γ、IL-17 和 IL-22 的表达来调节对微生物病原体的先天和适应性免疫。在此，我们定义了 IL-12 和 IL-23 在调节急性沙门氏菌感染期间宿主抵抗力和肠道炎症中的作用。我们发现，IL-23 单独对于防止细菌全身扩散是可有可无的，但与 IL-12 协同作用以获得最佳保护。IL-12 促进 NK 细胞产生 IFN-γ，这对于抵抗沙门氏菌以及诱导肠道炎症和上皮损伤是必需的。相比之下，IL-23 通过抑制 IL-12A 的表达来控制炎症的严重程度，从而减少 IFN-γ并防止过度的粘膜损伤。我们的研究表明，IL-23 是 IL-12 依赖性 IFN-γ 介导的肠道炎症的一种体内平衡调节剂。
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