TY - JOUR
T1 - T cells control chemokine secretion by keratinocytes
AU - Rauschenberger, Tabea
AU - Schmitt, Viola
AU - Azeem, Muhammad
AU - Klein-Hessling, Stefan
AU - Murti, Krisna
AU - Grän, Franziska
AU - Goebeler, Matthias
AU - Kerstan, Andreas
AU - Klein, Matthias
AU - Bopp, Tobias
AU - Serfling, Edgar
AU - Muhammad, Khalid
N1 - Publisher Copyright:
© 2019 Rauschenberger, Schmitt, Azeem, Klein®Hessling, Murti, Grän, Goebeler, Kerstan, Klein, Bopp, Serfling and Muhammad.
PY - 2019
Y1 - 2019
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.
AB - 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 - IFN
KW - Keratinocytes
KW - Lichen planus
KW - Nfatc1
KW - T cells
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U2 - 10.3389/fimmu.2019.01917
DO - 10.3389/fimmu.2019.01917
M3 - Article
C2 - 31447864
AN - SCOPUS:85071966685
SN - 1664-3224
VL - 10
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - AUG
M1 - 1917
ER -