Cutaneous inflammatory disorder in integrin alpha(E) (CD103)-deficient mice

The integrin alpha (E)beta (7) is thought to play an important role in the localization of mucosal, but not of cutaneous T lymphocytes, Thus, it was s urprising that 89% of adult alpha (-/-)(E) mice on the 129/Sv x BALB/c back ground developed inflammatory skin lesions without an apparent infectious e tiology, Skin inflammation correlated with alpha (E) deficiency in mice wit h a mixed 129/Sv x BALB/c background, but not in mice further backcrossed t o BALB/c and housed in a second animal facility. These studies suggested th at ag deficiency, in combination with other genetic and/or environmental fa ctors, is involved in lesion development. The lesions were infiltrated by C D4(+) T cells and neutrophils, and associated with increased expression of inflammatory cytokines. Furthermore, skin inflammation resulted from transf er of unfractionated alpha (-/-) splenocytes into scid/scid mice, but not f rom transfer of wild-type splenocytes, suggesting that the lesions resulted from immune dysregulation, We also studied the role of alpha (E)beta (7) i n a murine model of hyperproliferative inflammatory skin disorders that is induced by transfer of minor histocompatibility-mismatched CD4(+)/CD45RB(hi gh) T cells into scid/scid mice under specific environmental conditions. Un der housing conditions that were permissive for lesion development, transfe r of alpha (E)-deficient CD4(+)/CD45RB(high) T cells significantly exacerba ted the cutaneous lesions as compared with lesions observed in mice reconst ituted with wild-type donor cells. These experiments suggested that alpha ( E)-expressing cells play an important role during the course of cutaneous i nflammation. In addition, they suggest that alpha (E)beta (7) deficiency, i n combination with other genetic or environmental factors, is a risk factor for inflammatory skin disease.