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E (CD103)-Deficient Mice1
*
Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115;
Department of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany; and
Center for Animal Resources and Comparative Medicine, Harvard Medical School, Boston, MA 02115
The integrin 
E
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
E-/- mice on the 129/Sv x BALB/c
background developed inflammatory skin lesions without an apparent
infectious etiology. Skin inflammation correlated with 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 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
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
E7 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 E-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 E-expressing cells play an important role
during the course of cutaneous inflammation. In addition, they suggest
that E7 deficiency, in combination with
other genetic or environmental factors, is a risk factor for
inflammatory skin disease.
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