β7 Integrin Deficiency Suppresses B Cell Homing and Attenuates Chronic Ileitis in SAMP1/YitFc Mice

Abstract

Lymphocyte recruitment to intestinal tissues depends on β7 integrins. In this study, we studied disease severity and lymphocyte recruitment into the small intestine in SAMP1/YitFc mice, which develop chronic ileitis with similarity to human Crohn’s disease. To assess the role of β7 integrins in chronic ileitis, we generated SAMP1/YitFc lacking β7 integrins (SAMP1/YitFc Itgb7−/−) using a congenic strain developed via marker-assisted selection. We analyzed ileal inflammation in SAMP1/YitFc and SAMP1/YitFc Itgb7−/− mice by histopathology and the distribution of T and B lymphocytes in the mesenteric lymph nodes (MLNs) by flow cytometry. Short-term (18 h) adoptive transfer experiments were used to study the in vivo homing capacity of T and B lymphocytes. In both young (<20 wk) and old (20–50 wk) SAMP1/YitFc Itgb7−/− mice, ileitis was reduced by 30–50% compared with SAMP1/YitFc mice. SAMP1/YitFc Itgb7−/− mice showed a dramatic 67% reduction in the size of their MLNs, which was caused by a 85% reduction in lymphocyte numbers and reduced short-term B cell homing. Flow cytometric analysis revealed a highly significant decrease in the percentage of B cells in MLNs of SAMP1/YitFc Itgb7−/− mice. Cotransfer of SAMP1/YitFc MLN B cells but not SAMP1/YitFc Itgb7−/− MLN B cells along with CD4+ T cells resulted in exacerbated ileitis severity in SCID mice. Our findings suggest that β7 integrins play an essential role in spontaneous chronic ileitis in vivo by promoting homing of disease-exacerbating B cells to MLNs and other intestinal tissues.