82 : IL-36 promotes myeloid cell infiltration, activation and inflammatory activity in skin

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• 作者：Alex ; er M. Foster ; Jaymie Baliwag ; Cynthia S. Chen ; Andrew M. Guzman ; Stefan W. Stoll ; Johann E. Gudjonsson ; Nicole L. Ward ; Andrew Johnston
• 刊名：Cytokine
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：63
• 期：3
• 页码：262
• 全文大小：40 K

文摘

The IL-1 family members IL-36¦Á (IL-1F6), IL-36¦Â (IL-1F8) and IL-36¦Ã (IL-1F9) and the receptor antagonist IL-36Ra (IL-1F5) constitute a novel signaling system that is poorly understood. We now show that these cytokines have profound effects on the skin immune system. Treatment of human keratinocytes with IL-36¦Á or IL-36¦Â significantly increased the expression of CXCL1, CCL5, CCL20, CXCL10 and CCL22, potent chemotactic agents for activated leukocytes, and IL-36¦Á injected intradermally resulted in chemokine expression, leukocyte infiltration and acanthosis of mouse skin. Blood monocytes, myeloid dendritic cells (DC) and monocyte-derived DC (MO-DC) expressed IL-36R and responded to IL-36. In contrast, no direct effects of IL-36 on resting or activated human CD4+ or CD8+ T cells, or blood neutrophils, could be demonstrated. Monocytes expressed IL-1A, IL-1B and IL-6 mRNA and IL-1¦Â and IL-6 protein and mDC upregulated surface expression of CD83, CD86 and HLA-DR and secretion of IL-1¦Â and IL-6 after treatment with IL-36. Furthermore, IL-36¦Á-treated MO-DC enhanced allogeneic CD4+ T cell proliferation, demonstrating that IL-36 can stimulate the maturation and function of DC and drive T cell proliferation. These data indicate that IL-36 cytokines actively propagate skin inflammation via the activation of keratinocytes, antigen presenting cells and, indirectly, T cells.