Niess Jan H, Reinecker Hans-Christian
Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Curr Opin Gastroenterol. 2006 Jul;22(4):354-60. doi: 10.1097/01.mog.0000231807.03149.54.
Intestinal dendritic cells have emerged as key regulators of immunity to pathogens, oral tolerance and intestinal inflammation. Studies have begun to elucidate the regulatory mechanisms responsible for defining region- and compartment-specific phenotypes and functions of dendritic cells in mucosal tissues.
Specific subsets of dendritic cells appear to be associated with the various routes for antigen acquisition in the intestine. The constant sampling of intestinal antigenic content ensures establishment of tolerance to commensal bacteria and food antigens. Tolerance development to oral antigens is restricted to the mucosal immune system. Other advances have provided insight into the molecular basis of microbial recognition and innate immune responses by intestinal dendritic cells. Differences in the involvement of dendritic cells have begun to emerge in Crohn's disease and ulcerative colitis and link gene regulation in dendritic cells to therapeutic responses.
A major focus of mucosal immunology will be to understand how diverse dendritic cell subsets cooperate in regulating homeostasis and host defense in the different intestinal immune compartments. This will be pivotal to understanding how the mucosal immune system makes the distinction between commensal microbiota, pathogens and self antigens.
肠道树突状细胞已成为病原体免疫、口服耐受和肠道炎症的关键调节因子。研究已开始阐明负责定义黏膜组织中树突状细胞区域和隔室特异性表型及功能的调节机制。
特定亚群的树突状细胞似乎与肠道中抗原获取的各种途径相关。对肠道抗原成分的持续采样确保了对共生细菌和食物抗原的耐受性建立。对口服抗原的耐受性发展仅限于黏膜免疫系统。其他进展为肠道树突状细胞的微生物识别和固有免疫反应的分子基础提供了见解。在克罗恩病和溃疡性结肠炎中,树突状细胞参与情况的差异已开始显现,并将树突状细胞中的基因调控与治疗反应联系起来。
黏膜免疫学的一个主要重点将是了解不同的树突状细胞亚群如何在不同的肠道免疫隔室中协同调节内环境稳定和宿主防御。这对于理解黏膜免疫系统如何区分共生微生物群、病原体和自身抗原至关重要。