Journal
JOURNAL OF IMMUNOLOGY
Volume 184, Issue 5, Pages 2458-2467Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0902407
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Funding
- National Institutes of Health [AI031126, F30 DK082139, T32 AI007313, T32 CA009138]
- Harry Kay Chair in Biomedical Research at the University of Minnesota
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The alpha 4 beta 7 integrin promotes homing of T cells to intestinal sites. The alpha 4 integrin subunit that pairs with beta 7 integrin can also pair with beta 1 integrin. In this paper, we show that the preferential pairing of beta 1 integrin with alpha 4 integrin regulates the expression of alpha 4 beta 7 on T cells. In the absence of beta 1 integrin, naive mouse CD4 T cells have increased alpha 4 beta 7 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 beta 1 integrin causes the loss of alpha 4 beta 7 expression and decreased homing to PP. A similar upregulation of beta 1 integrin and suppression of alpha 4 beta 7 expression occurs rapidly after CD4 T cell activation. beta 1 integrin thus dominates beta 7 integrin for alpha A integrin pairing, thereby controlling the abundance of unpaired alpha 4 integrin. Increasing the abundance of alpha 4 integrin relative to beta 1 integrin is critical to retinoic acid-mediated expression of alpha 4 beta 7 integrin during T cell activation. In the absence of beta 1 integrin, endogenous Ag-specific CD4 T cells uniformly express high levels of alpha 4 beta 7 after Listeria monocytogenes infection. The resulting beta 1-deficient early memory T cells have decreased localization to the bone marrow and enhanced localization to PP after infection. Thus, the preferential association of beta 1 integrin with alpha 4 integrin suppresses alpha 4 beta 7 integrin expression and regulates the localization of memory CD4 T cells. The Journal of Immunology, 2010, 184: 2458-2467.
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