IL-36 Promotes Myeloid Cell Infiltration, Activation, and Inflammatory Activity in Skin

• DOI: 10.4049/jimmunol.1301481
• Publication Date: 2014-05-15T03:11:36Z
• Authors: Alexander M Foster; Jaymie Baliwag; Cynthia S Chen; Andrew M Guzman; Stefan W Stoll; Johann E Gudjonsson; Nicole L Ward; Andrew Johnston
• Keywords: CCL5; CCL20; CXCL1; CD86

The IL-1 family members IL-36α (IL-1F6), IL-36β (IL-1F8), and IL-36γ (IL-1F9) the receptor antagonist IL-36Ra (IL-1F5) constitute a novel signaling system that is poorly understood. We now show these cytokines have profound effects on skin immune system. Treatment of human keratinocytes with IL-36 significantly increased expression CXCL1, CXCL8, CCL3, CCL5, CCL20, potent chemotactic agents for activated leukocytes, injected intradermally resulted in chemokine expression, leukocyte infiltration, acanthosis mouse skin. Blood monocytes, myeloid dendritic cells (mDC), monocyte-derived DC (MO-DC) expressed IL-36R responded to IL-36. In contrast, no direct resting or CD4(+) CD8(+) T cells, blood neutrophils, could be demonstrated. Monocytes IL-1A, IL-1B, IL-6 mRNA IL-1β protein, mDC upregulated surface CD83, CD86, HLA-DR secretion after treatment Furthermore, IL-36α-treated MO-DC enhanced allogeneic cell proliferation, demonstrating can stimulate maturation function drive proliferation. These data indicate actively propagate inflammation via activation keratinocytes, APC, and, indirectly, cells.