L-selectin, α4β1, and α 4β7 integrins participate in CD4+ T cell recruitment to chronically inflamed small intestine

Jesús Rivera-Nieves, Timothy Olson, Giorgos Bamias, Anthony Bruce, Michael Solga, Robert F. Knight, Sharon Hoang, Fabio Cominelli, Klaus Ley

Research output: Contribution to journalArticlepeer-review

117 Scopus citations


CD4+ T cells are essential for development and perpetuation of Crohn's disease, a chronic immune-mediated condition that affects primarily the small intestine. Using novel models of Crohn's disease-like ileitis (i.e., SAMP1/YitFc and CD4+ T cell transfer models), we have begun to understand the adhesive pathways that mediate lymphocyte trafficking to the chronically inflamed small bowel. Expansion of the CD4/β7 + population and increased mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expression were observed within the intestinal lamina propria with disease progression. However, Ab blockade of the β7 integrin, the α4β7 heterodimer, MAdCAM-1, or L-selectin did not attenuate inflammation. Blockade of two pathways (L-selectin and MAdCAM-1 or α4 integrins) was required to improve ileitis. Further analyses showed that 55 ± 7% of the mesenteric lymph node α4β7CD4 expressed L-selectin. These L-selectin+ T cells were the main producers of TNF-α and the predominant ileitis-inducing subpopulation. Mechanistically, combined blockade of L-selectin and MAdCAM-1 depleted the intestinal lamina propria of CD4 + T cells that aberrantly coexpressed α4β 7 and α4β1 integrins, markedly decreasing local production of TNF-α and IFN-γ. Thus, pathogenic CD4+ T cells not only use the physiologic α4β 7/MAdCAM-1 pathway, but alternatively engage α 4β1 and L-selectin to recirculate to the chronically inflamed small intestine.

Original languageEnglish (US)
Pages (from-to)2343-2352
Number of pages10
JournalJournal of Immunology
Issue number4
StatePublished - Feb 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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