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Beta7 integrin deficiency suppresses B cell homing and attenuates chronic ileitis in SAMP1/YitFc mice.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2010 Nov 01; Vol. 185 (9), pp. 5561-8. Date of Electronic Publication: 2010 Oct 06. - Publication Year :
- 2010
-
Abstract
- Lymphocyte recruitment to intestinal tissues depends on β(7) 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 β(7) integrins in chronic ileitis, we generated SAMP1/YitFc lacking β(7) 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 β(7) 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.
- Subjects :
- Animals
B-Lymphocytes cytology
Chronic Disease
Flow Cytometry
Ileitis immunology
Ileitis metabolism
Integrin beta Chains metabolism
Intestine, Small immunology
Intestine, Small pathology
Lymph Nodes immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
T-Lymphocytes immunology
B-Lymphocytes immunology
Chemotaxis, Leukocyte immunology
Ileitis pathology
Integrin beta Chains immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 185
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 20926792
- Full Text :
- https://doi.org/10.4049/jimmunol.0903938