Control of α4β7 integrin expression and CD4 T cell homing by the β1 integrin subunit

Christopher C. DeNucci, Antonio J. Pagán, Jason S Mitchell, Yoji Shimizu

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The α4β7 integrin promotes homing of T cells to intestinal sites. The α4 integrin subunit that pairs with β7 integrin can also pair with β1 integrin. In this paper, we show that the preferential pairing of β1 integrin with α4 integrin regulates the expression of α4β7 on T cells. In the absence of β1 integrin, naive mouse CD4 T cells have increased α4β7 expression, resulting in increased adhesion to mucosal addressin cell adhesion molecule-1 and enhanced homing to Peyer's patches (PP). In a reciprocal manner, overexpression of β1 integrin causes the loss of α4β7 expression and decreased homing to PP. A similar upregulation of β1 integrin and suppression of α4β7 expression occurs rapidly after CD4 T cell activation. β1 integrin thus dominates β7 integrin for α4 integrin pairing, thereby controlling the abundance of unpaired α4 integrin. Increasing the abundance of α4 integrin relative to β1 integrin is critical to retinoic acid-mediated expression of α4β7 integrin during T cell activation. In the absence of β1 integrin, endogenous Ag-specific CD4 T cells uniformly express high levels of α4β7 after Listeria monocytogenes infection. The resulting β1-deficient early memory T cells have decreased localization to the bone marrow and enhanced localization to PP after infection. Thus, the preferential association of β1 integrin with α4 integrin suppresses α4β7 integrin expression and regulates the localization of memory CD4 T cells.

Original languageEnglish (US)
Pages (from-to)2458-2467
Number of pages10
JournalJournal of Immunology
Volume184
Issue number5
DOIs
StatePublished - Mar 1 2010

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Integrins
T-Lymphocytes
Peyer's Patches
Listeriosis
Cell Adhesion Molecules
Listeria monocytogenes
Tretinoin

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Control of α4β7 integrin expression and CD4 T cell homing by the β1 integrin subunit. / DeNucci, Christopher C.; Pagán, Antonio J.; Mitchell, Jason S; Shimizu, Yoji.

In: Journal of Immunology, Vol. 184, No. 5, 01.03.2010, p. 2458-2467.

Research output: Contribution to journalArticle

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