Premium
Statins can suppress DC‐mediated Th2 responses through the repression of OX40‐ligand and CCL17 expression
Author(s) -
InagakiKatashiba Noriko,
Ito Tomoki,
Inaba Muneo,
Azuma Yoshiko,
Tanaka Akihiro,
Phan Vien,
Kibata Kayoko,
Satake Atsushi,
Nomura Shosaku
Publication year - 2019
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201847992
Subject(s) - thymic stromal lymphopoietin , ccl17 , mevalonate pathway , biology , dendritic cell , cd86 , immunology , myeloid , cancer research , t cell , microbiology and biotechnology , inflammation , chemokine , reductase , immune system , chemokine receptor , biochemistry , enzyme
Abstract DCs and epithelial cell‐derived thymic stromal lymphopoietin (TSLP) have pivotal roles in allergic inflammation. TSLP stimulates myeloid DCs to express OX40‐ligand (OX40L) and CCL17, which trigger and maintain Th2 cell responses. We have previously shown that statins, which are HMG‐CoA reductase inhibitors, have the ability to suppress type I IFN production by plasmacytoid DCs. Here, we extended our previous work to examine the immunomodulatory effect of statins on allergic responses, particularly the TSLP‐dependent Th2 pathway induced by myeloid DCs. We found that treatment of TSLP‐stimulated DCs with either pitavastatin or simvastatin suppressed both the DC‐mediated inflammatory Th2 cell differentiation and CRTH2 + CD4 + memory Th2 cell expansion and also repressed the expressions of OX40L and CCL17 by DCs. These inhibitory effects of statins were mimicked by treatment with either a geranylgeranyl‐transferase inhibitor or Rho‐kinase inhibitor and were counteracted by the addition of mevalonate, suggesting that statins induce geranylgeranylated Rho inactivation through a mevalonate‐dependent pathway. We also found that statins inhibited the expressions of phosphorylated STA6 and NF‐κB‐p50 in TSLP‐stimulated DCs. This study identified a specific ability of statins to control DC‐mediated Th2 responses, suggesting their therapeutic potential for treating allergic diseases.