Department of Medicine, University of California, San Diego, La Jolla, California 92093-0063, USA.
Curr Opin Gastroenterol. 2010 Mar;26(2):109-15. doi: 10.1097/MOG.0b013e3283365279.
Coordination of innate and adaptive immunity is central to effective mucosal immune defense and homeostasis. The review discusses recent findings on two cytokines, IL-22 and IL-6, and their common signaling pathway, which bridge innate and adaptive immunity in the intestinal tract.
IL-22, a signature product of Th17 cells, is also secreted at functionally significant levels by innate immune cells, especially NKp44/NKp46-expressing natural killer (NK) cells and lymphoid tissue inducer cells after IL-23 stimulation. IL-22 acts primarily on epithelial cells and is overall protective, as its inhibition or loss exacerbates intestinal inflammation. Similarly, IL-6, secreted by macrophages, dendritic cells, epithelial cells, and T cells protects against mucosal damage, but it is also key in the development of Th17 cells, which mediate inflammatory and defensive responses in the intestine. Both cytokines activate STAT3 signaling, whose intestinal activities depend on the specific cell types involved. STAT3 in epithelial and myeloid cells mediates mucosa-protective and anti-inflammatory functions, whereas STAT3 in T cells promotes inflammation.
IL-22 and IL-6 are prime examples of cytokines that coordinate innate and adaptive immune responses in the intestine. They and their common signaling pathway, STAT3 can promote or protect against inflammation indicating that pharmacological manipulation for therapeutic purposes in intestinal inflammatory conditions may present special challenges.
先天免疫和适应性免疫的协调是有效黏膜免疫防御和稳态的核心。本文讨论了两种细胞因子白细胞介素-22（IL-22）和白细胞介素-6（IL-6）及其共同信号通路的最新发现，这些发现将肠道中的先天免疫和适应性免疫联系起来。
IL-22 是 Th17 细胞的标志性产物，在先天免疫细胞中也以功能上显著的水平分泌，特别是在 IL-23 刺激后，NKp44/NKp46 表达的自然杀伤（NK）细胞和淋巴组织诱导细胞。IL-22 主要作用于上皮细胞，总体上具有保护作用，因为其抑制或缺失会加剧肠道炎症。同样，巨噬细胞、树突状细胞、上皮细胞和 T 细胞分泌的白细胞介素-6（IL-6）可防止黏膜损伤，但它也是 Th17 细胞发育的关键，Th17 细胞介导肠道中的炎症和防御反应。这两种细胞因子都激活 STAT3 信号通路，其在肠道中的活性取决于涉及的特定细胞类型。STAT3 在上皮细胞和髓样细胞中介导黏膜保护和抗炎功能，而 STAT3 在 T 细胞中则促进炎症。
IL-22 和 IL-6 是协调肠道先天免疫和适应性免疫反应的细胞因子的典型代表。它们及其共同的信号通路 STAT3 可以促进或防止炎症，这表明在肠道炎症情况下，为治疗目的而进行药理学干预可能会带来特殊的挑战。
