Control of alpha4beta7 integrin expression and CD4 T cell homing by the beta1 integrin subunit.
The alpha4beta7 integrin promotes homing of T cells to intestinal sites. The alpha4 integrin subunit that pairs with beta7 integrin can also pair with beta1 integrin. In this paper, we show that the preferential pairing of beta1 integrin with alpha4 integrin regulates the expression of alpha4beta7 on T cells. In the absence of beta1 integrin, naive mouse CD4 T cells have increased alpha4beta7 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 beta1 integrin causes the loss of alpha4beta7 expression and decreased homing to PP. A similar upregulation of beta1 integrin and suppression of alpha4beta7 expression occurs rapidly after CD4 T cell activation. beta1 integrin thus dominates beta7 integrin for alpha4 integrin pairing, thereby controlling the abundance of unpaired alpha4 integrin. Increasing the abundance of alpha4 integrin relative to beta1 integrin is critical to retinoic acid-mediated expression of alpha4beta7 integrin during T cell activation. In the absence of beta1 integrin, endogenous Ag-specific CD4 T cells uniformly express high levels of alpha4beta7 after Listeria monocytogenes infection. The resulting beta1-deficient early memory T cells have decreased localization to the bone marrow and enhanced localization to PP after infection. Thus, the preferential association of beta1 integrin with alpha4 integrin suppresses alpha4beta7 integrin expression and regulates the localization of memory CD4 T cells.
DeNucci
Christopher C
CC
Department of Laboratory Medicine and Pathology, Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Pagán
Antonio J
AJ
Mitchell
Jason S
JS
Shimizu
Yoji
Y
D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D039441:Integrin alpha4 / Q000235:genetics / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010581:Peyer's Patches / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology
D019012:Integrin beta1; D016023:Integrins; C071777:integrin alpha4beta7; D039441:Integrin alpha4; D014212:Tretinoin