In:
The Journal of Immunology, The American Association of Immunologists, Vol. 171, No. 11 ( 2003-12-01), p. 5697-5706
Abstract:
In a CD18 hypomorphic polygenic PL/J mouse model, the severe reduction of CD18 (β2 integrin) to 2–16% of wild-type levels leads to the development of a psoriasiform skin disease. In this study, we analyzed the influence of reduced CD18 gene expression on T cell function, and its contribution to the pathogenesis of this disease. Both CD4+ and CD8+ T cells were significantly increased in the skin of affected CD18 hypomorphic mice. But only depletion of CD4+ T cells, and not the removal of CD8+ T cells, resulted in a complete clearance of the psoriasiform dermatitis. This indicates a central role of CD4+ T cells in the pathogenesis of this disorder, further supported by the detection of several Th1-like cytokines released predominantly by CD4+ T cells. In contrast to the CD18 hypomorphic mice, CD18 null mutants of the same strain did not develop the psoriasiform dermatitis. This is in part due to a lack of T cell emigration from dermal blood vessels, as experimental allergic contact dermatitis could be induced in CD18 hypomorphic and wild-type mice, but not in CD18 null mutants. Hence, 2–16% of CD18 gene expression is obviously sufficient for T cell emigration driving the inflammatory phenotype in CD18 hypomorphic mice. Our data suggest that the pathogenic involvement of CD4+ T cells depends on a gene dose effect with a reduced expression of the CD18 protein in PL/J mice. This murine inflammatory skin model may also have relevance for human polygenic inflammatory diseases.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.171.11.5697
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2003
detail.hit.zdb_id:
1475085-5
Permalink
