Cutaneous Inflammatory Disorder in Integrin αE (CD103)-Deficient Mice

• Published in: The Journal of immunology (1950) 2000-12, Vol.165 (11), p.6583-6589
• Main Authors: Schön, Michael P., Schön, Margarete, Warren, Henry B., Donohue, John P., Parker, Christina M.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.11.6583

The integrin αEβ7 is thought to play an important role in the localization of mucosal, but not of cutaneous T lymphocytes. Thus, it was surprising that 89% of adult αE−/− mice on the 129/Sv × BALB/c background developed inflammatory skin lesions without an apparent infectious etiology. Skin inflammation correlated with αE deficiency in mice with a mixed 129/Sv × BALB/c background, but not in mice further backcrossed to BALB/c and housed in a second animal facility. These studies suggested that αE deficiency, in combination with other genetic and/or environmental factors, is involved in lesion development. The lesions were infiltrated by CD4+ T cells and neutrophils, and associated with increased expression of inflammatory cytokines. Furthermore, skin inflammation resulted from transfer of unfractionated αE−/− splenocytes into scid/scid mice, but not from transfer of wild-type splenocytes, suggesting that the lesions resulted from immune dysregulation. We also studied the role of αEβ7 in a murine model of hyperproliferative inflammatory skin disorders that is induced by transfer of minor histocompatibility-mismatched CD4+/CD45RBhigh T cells into scid/scid mice under specific environmental conditions. Under housing conditions that were permissive for lesion development, transfer of αE-deficient CD4+/CD45RBhigh T cells significantly exacerbated the cutaneous lesions as compared with lesions observed in mice reconstituted with wild-type donor cells. These experiments suggested that αE-expressing cells play an important role during the course of cutaneous inflammation. In addition, they suggest that αEβ7 deficiency, in combination with other genetic or environmental factors, is a risk factor for inflammatory skin disease.