CONTROL OF α4β7 INTEGRIN EXPRESSION AND CD4 T CELL HOMING BY THE β1 INTEGRIN SUBUNIT1

• Published in: The Journal of immunology (1950) Vol. 184; no. 5; pp. 2458 - 2467
• Main Authors: DeNucci, Christopher C., Pagan, Antonio J., Mitchell, Jason S., Shimizu, Yoji
• Format: Journal Article
• Language: English
• Published: 29.01.2010
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0902407

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. Here, 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, naïve mouse CD4 T cells have increased α4β7 expression, resulting in increased adhesion to MAdCAM-1 and enhanced homing to Peyer’s patches. In a reciprocal manner, over-expression of β1 integrin causes the loss of α4β7 expression and decreased homing to Peyer’s patches. A similar upregulation of β1 integrin and suppression of α4β7 expression occurs rapidly following 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 antigen-specific CD4 T cells uniformly express high levels of α4β7 following Listeria monocytogenes infection. The resulting β1-deficient early memory T cells have decreased localization to the bone marrow and enhanced localization to Peyer’s patches following infection. Thus, the preferential association of β1 integrin with α4 integrin suppresses α4β7 integrin expression and regulates the localization of memory CD4 T cells.