Mizoguchi Atsushi, Ogawa Atsushiro, Takedatsu Hidetoshi, Sugimoto Ken, Shimomura Yasuyo, Shirane Katsunori, Nagahama Kiyotaka, Nagaishi Takashi, Mizoguchi Emiko, Blumberg Richard S, Bhan Atul K
Department of Pathology Service,Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
J Clin Invest. 2007 Mar;117(3):605-15. doi: 10.1172/JCI30150. Epub 2007 Feb 22.
Granulomas represent a localized inflammatory reaction that is characteristically observed in many inflammatory conditions. However, the mechanisms of granuloma formation have not been fully defined. Herein we demonstrate, by using experimental models of intestinal inflammation, that a unique CD11c+ DC-like cell subset that exhibits phenotypic and functional features of immature myeloid DCs and is characterized by the expression of a macrophage marker (F4/80) produces large amounts of IL-23 and directly induces the development of granulomas under a Th1-predominant intestinal inflammatory condition. Importantly, both IL-4 and IgG contribute to the suppression of F4/80+ DC-like cell-mediated granuloma formation by regulating the function and differentiation of this cell subset. In addition, enteric flora is required for the F4/80+ DC-like cell-mediated granuloma formation. Collectively, our data provide what we believe are novel insights into the involvement of F4/80+ DC-like cells in intestinal granuloma formation and demonstrate the role of host (IL-4 and IgG) and environmental (enteric flora) factors that regulate this function.
肉芽肿代表一种局部炎症反应，在许多炎症性疾病中均可典型地观察到。然而，肉芽肿形成的机制尚未完全明确。在此，我们通过使用肠道炎症实验模型证明，一种独特的CD11c⁺ 树突状细胞样细胞亚群，其表现出未成熟髓样树突状细胞的表型和功能特征，并以巨噬细胞标志物（F4/80）的表达为特征，在以Th1为主的肠道炎症条件下可产生大量白细胞介素-23并直接诱导肉芽肿的形成。重要的是，白细胞介素-4和免疫球蛋白G均通过调节该细胞亚群的功能和分化，有助于抑制F4/80⁺ 树突状细胞样细胞介导的肉芽肿形成。此外，肠道菌群是F4/80⁺ 树突状细胞样细胞介导的肉芽肿形成所必需的。总体而言，我们的数据为F4/80⁺ 树突状细胞样细胞参与肠道肉芽肿形成提供了我们认为是新颖的见解，并证明了宿主（白细胞介素-4和免疫球蛋白G）和环境（肠道菌群）因素调节该功能的作用。
