TY - JOUR A1 - Rauschenberger, Tabea A1 - Schmitt, Viola A1 - Azeem, Muhammad A1 - Klein-Hessling, Stefan A1 - Murti, Krisna A1 - Grän, Franziska A1 - Goebeler, Matthias A1 - Kerstan, Andreas A1 - Klein, Matthias A1 - Bopp, Tobias A1 - Serfling, Edgar A1 - Muhammad, Khalid T1 - T cells control chemokine secretion by keratinocytes JF - Frontiers in Immunology N2 - The massive infiltration of lymphocytes into the skin is a hallmark of numerous human skin disorders. By co-culturing murine keratinocytes with splenic T cells we demonstrate here that T cells affect and control the synthesis and secretion of chemokines by keratinocytes. While pre-activated CD8\(^+\)T cells induce the synthesis of CXCL9 and CXCL10 in keratinocytes and keep in check the synthesis of CXCL1, CXCL5, and CCL20, keratinocytes dampen the synthesis of CCL3 and CCL4 in pre-activated CD8\(^+\)T cells. One key molecule is IFN-γ that is synthesized by CD8\(^+\)T cells under the control of NFATc1 and NFATc2. CD8\(^+\)T cells deficient for both NFAT factors are unable to induce CXCL9 and CXCL10 expression. In addition, CD8\(^+\)T cells induced numerous type I IFN-inducible “defense genes” in keratinocytes encoding the PD1 and CD40 ligands, TNF-α and caspase-1. The enhanced expression of type I IFN-inducible genes resembles the gene expression pattern at the dermal/epidermal interface in lichen planus, an inflammatory T lymphocyte-driven skin disease, in which we detected the expression of CXCL10 in keratinocytes in close vicinity to the infiltration front of T cells. These data reflect the multifaceted interplay of lymphocytes with keratinocytes at the molecular level. KW - chemokine KW - keratinocytes KW - IFN KW - lichen planus KW - T cells KW - Nfatc1 Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195695 SN - 1664-3224 VL - 10 IS - 1917 ER -