title: Cutaneous inflammatory disorder in integrin alphaE (CD103)-deficient mice.
abstract: 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 surprising that 89% of adult alpha(E)(-/-) mice on the 129/Sv x BALB/c background developed inflammatory skin lesions without an apparent infectious etiology. Skin inflammation correlated with alpha(E) deficiency in mice with a mixed 129/Sv x BALB/c background, but not in mice further backcrossed to BALB/c and housed in a second animal facility. These studies suggested that alpha(E) 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 alpha(E)(-/-) 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 alpha(E)beta(7) in a murine model of hyperproliferative inflammatory skin disorders that is induced by transfer of minor histocompatibility-mismatched CD4(+)/CD45RB(high) T cells into scid/scid mice under specific environmental conditions. Under housing conditions that were permissive for lesion development, transfer of alpha(E)-deficient CD4(+)/CD45RB(high) T cells significantly exacerbated the cutaneous lesions as compared with lesions observed in mice reconstituted with wild-type donor cells. These experiments suggested that alpha(E)-expressing cells play an important role during the course of cutaneous inflammation. In addition, they suggest that alpha(E)beta(7) deficiency, in combination with other genetic or environmental factors, is a risk factor for inflammatory skin disease.
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Schön
authors.forename: M
authors.initials: M
authors.lastname: Schön
authors.forename: H B
authors.initials: HB
authors.lastname: Warren
authors.forename: J P
authors.initials: JP
authors.lastname: Donohue
authors.forename: C M
authors.initials: CM
authors.lastname: Parker
mesh_terms: D019264:Adoptive Transfer; D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D039001:Integrin alpha Chains; D016023:Integrins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D011565:Psoriasis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D012867:Skin / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000637:transplantation
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; D016023:Integrins; C091367:alpha E integrins; C070709:integrin alphaEbeta7