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

Abstract

IL-17 is a critical factor in the pathogenesis of psoriasis and other inflammatory diseases. The impact of γδ T cells, accounting for an important source of IL-17 in acute murine IL-23- and imiquimod-induced skin inflammation, in human psoriasis is still unclear. Using the polygenic CD18(hypo) PL/J psoriasis mouse model spontaneously developing chronic psoriasiform dermatitis due to reduced CD18/β2 integrin expression to 2-16% of wild-type levels, we investigated in this study the influence of adhesion molecule expression on generation of inflammatory γδ T cells and analyzed the occurrence of IL-17-producing γδ and CD4(+) T cells at different disease stages. Severity of CD18(hypo) PL/J psoriasiform dermatitis correlated with a loss of skin-resident Vγ5(+) T cells and concurrent skin infiltration with IL-17(+), IL-22(+), and TNF-α(+) γδTCR(low) cells preceded by increases in Vγ4(+) T cells in local lymph nodes. In vitro, reduced CD18 levels promoted expansion of inflammatory memory-type γδ T cells in response to IL-7. Similar to IL-17 or IL-23/p19 depletion, injection of diseased CD18(hypo) PL/J mice with anti-γδTCR Abs significantly reduced skin inflammation and largely eliminated pathological γδ and CD4(+) T cells. Moreover, CD18(hypo) γδ T cells induced allogeneic CD4(+) T cell responses more potently than CD18(wt) counterparts and, upon adoptive transfer, triggered psoriasiform dermatitis in susceptible hosts. These results demonstrate a novel function of reduced CD18 levels in generation of pathological γδ T cells that was confirmed by detection of increases in CD18(low) γδ T cells in psoriasis patients and may also have implications for other inflammatory diseases.

• Authors: Martina Gatzka, Adelheid Hainzl, Thorsten Peters, Kamayani Singh, Alpaslan Tasdogan, Meinhard Wlaschek, Karin Scharffetter-Kochanek
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 191 Issue 11 Pg. 5477-88 (Dec 01 2013) ISSN: 1550-6606 [Electronic] United States
• PMID: 24190659 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD18 Antigens
• Cytokines
• Inflammation Mediators
• Receptors, Antigen, T-Cell, gamma-delta

Topics

• Adoptive Transfer
• Animals
• CD18 Antigens (genetics, metabolism)
• CD4-Positive T-Lymphocytes (immunology)
• Cell Communication
• Cell Proliferation
• Cells, Cultured
• Chronic Disease
• Cytokines (immunology)
• Dermatitis (immunology)
• Disease Models, Animal
• Disease Susceptibility
• Down-Regulation
• Humans
• Inflammation Mediators (immunology)
• Mice
• Mice, Inbred Strains
• Psoriasis (immunology)
• Receptors, Antigen, T-Cell, gamma-delta (metabolism)
• T-Lymphocyte Subsets (immunology)