TY - JOUR
AU - Parker, Christina M.
AB - It has been thought that lymphocytes play an important role in the pathogenesis of inflammatory bowel diseases (IBDs), based on the association of IBDs with other autoimmune manifestations and the association of IBDs with certain major histocompatibility complex alleles. Interestingly, the transfer of CD4+/CD45RBhigh/splenocytes into severe combined immunodeficient (SCID) mice results in severe transmural intestinal inflammation, demonstrating that activated T lymphocytes can induce intestinal inflammation in the absence of a primary abnormality of the intestinal tract (1). By identifying molecules important in the site-specific localization or function of mucosal T lymphocytes, it may be possible to interrupt mucosal lymphocyte localization or function and thus to reduce intestinal inflammation in IBD patients without affecting immunity in other sites. Many members of the integrin family of adhesion molecules are expressed on lymphocytes, where they function to bind endothelial and epithelial cell surface molecules, and extracellular matrix components. Integrins are important in lymphocyte development, activation, homing, and migration. Integrins specially expressed on mucosal lymphocytes are candidates to perform mucosa-specific functions which might be interrupted to treat IBDs. One such integrin is the human mucosal lymphocyte-1 (HML-1) antigen, expressed on >90% of intestinal intraepithelial lymphocytes (iIEL) and on 40-50% of lamina propria lymphocytes but on <5% of peripheral blood lymphocytes. This αEβ7 integrin complex (2) mediates adhesion of in vitro cultured iIEL lines to epithelial cells through its interaction with the epithelial cell adhesion molecule E-cadherin (3). It has been proposed that αEβ7 plays a role in retaining lymphocytes within the epithelium (3). This integrin also appears to send a signal to the T cell that is important in its activation. Thus, the αEβ7 integrin probably is important in the localization or function of mucosal lymphocytes. In recent studies, we have produced αE/null mice by targeted disruption of the αE encoding gene. Studies of these animals and using adoptive transfer experiments reveal an important role of the αE integrin in intestinal lymphocyte localization. In addition, experiments indicate that αE-deficient T lymphocytes are less efficient in generating the CD4+/CD45RBhigh transfer model of IBD. These observations suggest that interrupting the function of αE may alleviate intestinal inflammation in patients with IBDs. References 1. Powrie F, Mason D. Ox22high CD4+ T cells induce wasting disease with multiple organ pathology: prevention of the OX22-low subset. J Exp Med 1990;172:1701-8. 2. Parker CM, Cepek K, Russell GJ, et al. A family of β7 integrins on human mucosal lymphocytes. Proc Natl Acad Sci USA 1992;89:1924-8. 3. Cepek KL, Shaw SK, Parker CM, et al. Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the alpha(E)beta(7) integrin. Nature 1994;372:190-3. © 1997 Crohn's & Colltls Foundatmn of Amcrlca. Inc
TI - Integrin αE Deficient Mice Reveal a Role of αE Intestinal Inflammation
JO - Inflammatory Bowel Diseases
DO - 10.1097/00054725-199706000-00013
DA - 1997-05-01
UR - https://www.deepdyve.com/lp/oxford-university-press/integrin-e-deficient-mice-reveal-a-role-of-e-intestinal-inflammation-cQcgdDFKm3
SP - 147
EP - 147
VL - 3
IS - 2
DP - DeepDyve
ER -