Leon Francisco, Smythies Lesley E, Smith Phillip D, Kelsall Brian L
Laboratory of Molecular Immunology, NIAID, National Institutes of Health, Bethesda, MD, USA.
Adv Exp Med Biol. 2006;579:117-32. doi: 10.1007/0-387-33778-4_8.
In conclusion, during inflammation, DCs are likely activated by inflammatory signals and induced to migrate to T cell zones of organized lymphoid tissues where the cells induce T cell responses. In addition to their established role in T cell priming and the induction of tolerance, DCs may act to enhance (or possibly suppress) T cell responses at sites of mucosal inflammation. Determining the importance of DCs in this regard, as well as establishing a potential role for DCs in continuous activation of naive or central memory cells in lymph nodes draining inflammatory sites, will elucidate the role of DCs as a potential therapeutic target for chronic inflammatory diseases, like IBD. Resident intestinal macrophages are noninflammatory and do not efficiently present antigens to intestinal T cells, yet are avidly phagocytic and able to kill internalized organisms. During intestinal inflammation, monocytes are recruited from the blood, become inflammatory macrophages in the inflamed tissue, and are major contributors to tissue destruction and perpetuation of inflammation via their production of chemokines and pro-inflammatory cytokines. Macrophages may also contribute directly to DC activation and maturation, which would drive DCs to present antigens from the bacterial flora to T cells locally within tissue or to more efficiently traffic to T cell zones of lymphoid tissue. Thus, DCs and macrophages have evolved functional niches that promote cooperation in the prevention of untoward intestinal inflammation in the steady state and in the eradication of invasive microorganisms during infection. The balance between suppressing inflammation and promoting host defense is altered in humans with IBD allowing a persistent inflammatory response to commensal bacteria. Based on studies from animal models, the pathogenesis of IBD likely involves either the lack of appropriate regulation from T cells, or an over-production of effector T cells. The end result of these potential mechanisms is the abnormal induction and/or survival of effector T cells and the production of factors such as cytokines by inflammatory macrophages and neutrophils that result in tissue destruction. The destructive process likely involves normally tolerizing DCs, which in the microenvironment of the inflamed mucosa activate T cell responses to normal flora in both draining lymphoid tissues and at sites of inflammation, with macrophages and neutrophils contributing the bulk of inflammatory and destructive cytokines.
总之，在炎症过程中，树突状细胞（DCs）可能被炎症信号激活，并被诱导迁移至有组织的淋巴组织的T细胞区，在那里这些细胞诱导T细胞反应。除了在T细胞致敏和诱导耐受性方面已确定的作用外，DCs可能在黏膜炎症部位增强（或可能抑制）T细胞反应。确定DCs在这方面的重要性，以及确定DCs在引流炎症部位的淋巴结中持续激活幼稚或中枢记忆细胞的潜在作用，将阐明DCs作为慢性炎症性疾病（如炎症性肠病，IBD）潜在治疗靶点的作用。驻留的肠道巨噬细胞无炎症性，不能有效地将抗原呈递给肠道T细胞，但具有活跃的吞噬作用，能够杀死内化的微生物。在肠道炎症期间，单核细胞从血液中募集，在炎症组织中成为炎症性巨噬细胞，并且通过产生趋化因子和促炎细胞因子，它们是组织破坏和炎症持续存在的主要促成因素。巨噬细胞也可能直接促成DCs的激活和成熟，这将促使DCs在组织内局部将来自细菌菌群的抗原呈递给T细胞，或更有效地转运至淋巴组织的T细胞区。因此，DCs和巨噬细胞已经形成了功能性生态位，在稳态下促进合作以预防不良的肠道炎症，并在感染期间根除侵入性微生物。在患有IBD的人类中，抑制炎症和促进宿主防御之间的平衡被改变，从而允许对共生细菌产生持续的炎症反应。基于动物模型的研究，IBD的发病机制可能涉及T细胞缺乏适当调节，或效应T细胞产生过多。这些潜在机制的最终结果是效应T细胞的异常诱导和/或存活，以及炎症性巨噬细胞和中性粒细胞产生诸如细胞因子等因子，从而导致组织破坏。破坏过程可能涉及通常具有耐受性的DCs，在炎症黏膜的微环境中，它们在引流淋巴组织和炎症部位激活对正常菌群的T细胞反应，而巨噬细胞和中性粒细胞则产生大部分炎症和破坏性细胞因子。
