Reduction of CD18 promotes expansion of inflammatory γδ T cells collaborating with CD4+ T cells in chronic murine psoriasiform dermatitis.

Reduction of CD18 Promotes Expansion of Inflammatory gd T Cells Collaborating with CD4 T Cells in Chronic Murine Psoriasiform Dermatitis

CD4+ T cell-associated pathophysiology critically depends on CD18 gene dose effects in a murine model of psoriasis.

In a CD18 hypomorphic polygenic PL/J mouse model, the severe reduction of CD18 (beta(2) 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...

Antibodies to complement receptor 3 treat established inflammation in murine models of colitis and a novel model of psoriasiform dermatitis.

Prior studies indicated the ability of Abs to complement receptor 3 (CR3, CD11b/CD18) to suppress the production of IL-12 from immune cells. Therefore, we tested the ability of an anti-CR3 Ab (clone M1/70) to treat established IL-12-dependent Th1-mediated inflammation in murine models. Systemic administration of anti-CR3 significantly ameliorated established intestinal inflammation following th...

Epidermal CCR6+ γδ T cells are major producers of IL-22 and IL-17 in a murine model of psoriasiform dermatitis.

Cytokine components of Th17 pathway play vital roles in human psoriasis. Although much is known about TCR αβ T cells in psoriasis, the role of unconventional T cells, including γδ T cells, is unclear. In this study, using an IL-23 skin injection model of psoriasiform dermatitis in mice, we demonstrate that IL-22, IL-17A, and the IL-23R were highly enriched in a population of CCR6(+), TCR γδ-low...

A 9-centimorgan interval of chromosome 10 controls the T cell-dependent psoriasiform skin disease and arthritis in a murine psoriasis model.

Psoriasis is a complex genetic disease of unresolved pathogenesis with both heritable and environmental factors contributing to onset and severity. In addition to a disfiguring skin inflammation, approximately 10-40% of psoriasis patients suffer from destructive joint involvement. Previously, we reported that the CD18 hypomorphic PL/J mouse carrying a mutation resulting in reduced expression of...