HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rivera-Nieves, J. Articles by Ley, K. Search for Related Content PubMed PubMed Citation Articles by Rivera-Nieves, J. Articles by Ley, K.

L-Selectin, ₄₁, and ₄₇ Integrins Participate in CD4⁺ T Cell Recruitment to Chronically Inflamed Small Intestine¹

Jesús Rivera-Nieves^2,*, Timothy Olson, Giorgos Bamias^*, Anthony Bruce, Michael Solga, Robert F. Knight^*, Sharon Hoang^*, Fabio Cominelli^* and Klaus Ley^,,¶

^* Digestive Health Center of Excellence, Molecular Physiology and Biological Physics, Cardiovascular Research Center, Flow Cytometry Core Facility, and ^¶ Departments of Biomedical Engineering, University of Virginia Health Sciences Center, Charlottesville, VA 22908

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 CD4/₇⁺ 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 ₇ integrin, the ₄₇ heterodimer, MAdCAM-1, or L-selectin did not attenuate inflammation. Blockade of two pathways (L-selectin and MAdCAM-1 or ₄ integrins) was required to improve ileitis. Further analyses showed that 55 ± 7% of the mesenteric lymph node ₄₇⁺CD4 expressed L-selectin. These L-selectin⁺ T cells were the main producers of TNF- 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 ₄₇ and ₄₁ integrins, markedly decreasing local production of TNF- and IFN-. Thus, pathogenic CD4⁺ T cells not only use the physiologic ₄₇/MAdCAM-1 pathway, but alternatively engage ₄₁ and L-selectin to recirculate to the chronically inflamed small intestine.

This article has been cited by other articles:

				E. Smith, M. A. Stark, A. Zarbock, T. L. Burcin, A. C. Bruce, D. Vaswani, P. Foley, and K. Ley IL-17A Inhibits the Expansion of IL-17A-Producing T Cells in Mice through "Short-Loop" Inhibition via IL-17 Receptor J. Immunol., July 15, 2008; 181(2): 1357 - 1364. [Abstract] [Full Text] [PDF]

				A. Miles, E. Liaskou, B. Eksteen, P. F. Lalor, and D. H. Adams CCL25 and CCL28 promote {alpha}4{beta}7-integrin-dependent adhesion of lymphocytes to MAdCAM-1 under shear flow Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1257 - G1267. [Abstract] [Full Text] [PDF]

				E. Smith, A. Zarbock, M. A. Stark, T. L. Burcin, A. C. Bruce, P. Foley, and K. Ley IL-23 Is Required for Neutrophil Homeostasis in Normal and Neutrophilic Mice J. Immunol., December 15, 2007; 179(12): 8274 - 8279. [Abstract] [Full Text] [PDF]

				M. Saruta, Q. T. Yu, A. Avanesyan, P. R. Fleshner, S. R. Targan, and K. A. Papadakis Phenotype and Effector Function of CC Chemokine Receptor 9-Expressing Lymphocytes in Small Intestinal Crohn's Disease J. Immunol., March 1, 2007; 178(5): 3293 - 3300. [Abstract] [Full Text] [PDF]

				J. Rivera-Nieves, T. L. Burcin, T. S. Olson, M. A. Morris, M. McDuffie, F. Cominelli, and K. Ley Critical role of endothelial P-selectin glycoprotein ligand 1 in chronic murine ileitis J. Exp. Med., April 17, 2006; 203(4): 907 - 917. [Abstract] [Full Text] [PDF]

				S. Ghosh, A. A. Chackerian, C. M. Parker, C. M. Ballantyne, and S. M. Behar The LFA-1 adhesion molecule is required for protective immunity during pulmonary Mycobacterium tuberculosis infection. J. Immunol., April 15, 2006; 176(8): 4914 - 4922. [Abstract] [Full Text] [PDF]

				D. Fairweather, S. Frisancho-Kiss, D. B. Njoku, J. F. Nyland, Z. Kaya, S. A. Yusung, S. E. Davis, J. A. Frisancho, M. A. Barrett, and N. R. Rose Complement Receptor 1 and 2 Deficiency Increases Coxsackievirus B3-Induced Myocarditis, Dilated Cardiomyopathy, and Heart Failure by Increasing Macrophages, IL-1beta, and Immune Complex Deposition in the Heart J. Immunol., March 15, 2006; 176(6): 3516 - 3524. [Abstract] [Full Text] [PDF]

				G. Bamias, M. R. Nyce, S. A. De La Rue, and F. Cominelli New Concepts in the Pathophysiology of Inflammatory Bowel Disease Ann Intern Med, December 20, 2005; 143(12): 895 - 904. [Full Text] [PDF]