Senior Scholars Program

Title

Endoscopic photoconversion reveals unexpectedly broad leukocyte trafficking to and from the gut

UMMS Affiliation

School of Medicine; Senior Scholars Program

Faculty Advisor

Ralph Weissleder (Massachusetts General Hospital)

Date

5-6-2014

Document Type

Article

Medical Subject Headings

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

Disciplines

Immunity | Immunopathology

Abstract

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.

Rights and Permissions

Citation: 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

Related Resources

Link to article in PubMed

Comments

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.

Publisher

National Academy of Sciences

PubMed ID

24753589