Endoscopic photoconversion reveals unexpectedly broad leukocyte trafficking to and from the gut
School of Medicine; Senior Scholars Program
Ralph Weissleder (Massachusetts General Hospital)
Adaptive Immunity; Animals; Antigens, CD45; Arthritis, Experimental; Cell Movement; Digestive System; Genes, Reporter; Immunity, Innate; Leukocytes; Luminescent Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, Transgenic; Microbiota; Photochemical Processes
Immunity | Immunopathology
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.
DOI of Published Version
Morton AM, Sefik E, Upadhyay R, Weissleder R, Benoist C, Mathis D. Endoscopic photoconversion reveals unexpectedly broad leukocyte trafficking to and from the gut. Proc Natl Acad Sci U S A. 2014 May 6;111(18):6696-701. doi:10.1073/pnas.1405634111. Epub 2014 Apr 21. PubMed PMID: 24753589; PubMed Central PMCID: PMC4020091. Link to article on publisher's website
Proceedings of the National Academy of Sciences of the United States of America
Morton, Angela M.; Sefik, Esen; Upadhyay, Rabi; Weissleder, Ralph; Benoist, Christophe; and Mathis, Diane, "Endoscopic photoconversion reveals unexpectedly broad leukocyte trafficking to and from the gut" (2014). University of Massachusetts Medical School. Senior Scholars Program. Paper 220.