Details

Autor(en) / Beteiligte

• Gatzka, Martina
• Hainzl, Adelheid
• Peters, Thorsten
• Singh, Kamayani
• Tasdogan, Alpaslan
• Wlaschek, Meinhard
• Scharffetter-Kochanek, Karin

Titel

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

Ist Teil von

• The Journal of immunology (1950), 2013-12, Vol.191 (11), p.5477-5488

Erscheinungsjahr

2013

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• IL-17 is a critical factor in the pathogenesis of psoriasis and other inflammatory diseases. The impact of gamma delta 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 CD18hypo PL/J psoriasis mouse model spontaneously developing chronic psoriasiform dermatitis due to reduced CD18/ beta 2 integrin expression to 2-16% of wild-type levels, we investigated in this study the influence of adhesion molecule expression on generation of inflammatory gamma delta T cells and analyzed the occurrence of IL-17-producing gamma delta and CD4+ T cells at different disease stages. Severity of CD18hypo PL/J psoriasiform dermatitis correlated with a loss of skin-resident V gamma 5+ T cells and concurrent skin infiltration with IL-17+, IL-22+, and TNF- alpha + gamma delta TCRlow cells preceded by increases in V gamma 4+ T cells in local lymph nodes. In vitro, reduced CD18 levels promoted expansion of inflammatory memory-type gamma delta T cells in response to IL-7. Similar to IL-17 or IL-23/p19 depletion, injection of diseased CD18hypo PL/J mice with anti- gamma delta TCR Abs significantly reduced skin inflammation and largely eliminated pathological gamma delta and CD4+ T cells. Moreover, CD18hypo gamma delta T cells induced allogeneic CD4+ T cell responses more potently than CD18wt 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 gamma delta T cells that was confirmed by detection of increases in CD18low gamma delta T cells in psoriasis patients and may also have implications for other inflammatory diseases.