Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 2014 May 6;111(18):6696-701. doi: 10.1073/pnas.1405634111. Epub 2014 Apr 21.
Given mounting evidence of the importance of gut-microbiota/immune-cell interactions in immune homeostasis and responsiveness, surprisingly little is known about leukocyte movements to, and especially from, the gut. We address this topic in a minimally perturbant manner using Kaede transgenic mice, which universally express a photoconvertible fluorescent reporter. Transcutaneous exposure of the cervical lymph nodes to violet light permitted punctual tagging of immune cells specifically therein, and subsequent monitoring of their immigration to the intestine; endoscopic flashing of the descending colon allowed specific labeling of intestinal leukocytes and tracking of their emigration. Our data reveal an unexpectedly broad movement of leukocyte subsets to and from the gut at steady state, encompassing all lymphoid and myeloid populations examined. Nonetheless, different subsets showed different trafficking proclivities (e.g., regulatory T cells were more restrained than conventional T cells in their exodus from the cervical lymph nodes). The novel endoscopic approach enabled us to evidence gut-derived Th17 cells in the spleens of K/BxN mice at the onset of their genetically determined arthritis, thereby furnishing a critical mechanistic link between the intestinal microbiota, namely segmented filamentous bacteria, and an extraintestinal autoinflammatory disease.
越来越多的证据表明肠道微生物群/免疫细胞相互作用对于免疫稳态和反应性至关重要，但人们对白细胞向肠道的迁移，特别是从肠道迁移的过程知之甚少。我们使用 Kaede 转基因小鼠以最小干扰的方式解决了这个问题，该小鼠普遍表达可光转化的荧光报告基因。通过对颈部淋巴结进行经皮紫光照射，可以特异性标记其中的免疫细胞，然后监测它们向肠道的迁移；对降结肠进行内镜闪烁可以特异性标记肠道白细胞并追踪它们的迁出。我们的数据显示，在稳态下，白细胞亚群出人意料地广泛迁移到肠道，包括所有检查的淋巴样和髓样细胞群。尽管如此，不同的亚群表现出不同的迁移倾向（例如，调节性 T 细胞从颈部淋巴结迁出的倾向比传统 T 细胞小）。这种新的内镜方法使我们能够在 K/BxN 小鼠关节炎发病时在其脾脏中发现源自肠道的 Th17 细胞，从而为肠道微生物群（即分节丝状细菌）和肠外自身炎症性疾病之间提供了一个关键的机制联系。
