Endoscopic photoconversion reveals unexpectedly broad leukocyte trafficking to and from the gut
Faculty Advisor
Ralph Weissleder (Massachusetts General Hospital)Document Type
Journal ArticlePublication Date
2014-05-06Keywords
Adaptive ImmunityAnimals
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
Metadata
Show full item recordAbstract
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.Source
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 websiteDOI
10.1073/pnas.1405634111Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49277PubMed ID
24753589Notes
Rabi Upadhyay participated in this study as a medical student as part of the Senior Scholars research program at the University of Massachusetts Medical School.
Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1073/pnas.1405634111