TY - JOUR
T1 - The Enzyme Cyp26b1 mediates inhibition of mast cell activation by fibroblasts to maintain skin-barrier homeostasis
AU - Kurashima, Yosuke
AU - Amiya, Takeaki
AU - Fujisawa, Kumiko
AU - Shibata, Naoko
AU - Suzuki, Yuji
AU - Kogure, Yuta
AU - Hashimoto, Eri
AU - Otsuka, Atsushi
AU - Kabashima, Kenji
AU - Sato, Shintaro
AU - Sato, Takeshi
AU - Kubo, Masato
AU - Akira, Shizuo
AU - Miyake, Kensuke
AU - Kunisawa, Jun
AU - Kiyono, Hiroshi
N1 - Funding Information:
We thank H. Suto (Atopy Research Center, Juntendo University, Tokyo) for providing Kit W-sh/W-sh mice, and S. Nakae (University of Tokyo) for advice on analyzing Kit W-sh/W-sh mice. We also thank Y. Yokota (School of Medicine, University of Fukui, Fukui) for providing Id2 −/− mice. This work was supported by grants from the Ministry of Education, Science, Sports, and Technology of Japan (Grant-in Aid for Scientific Research S [H.K.] for Scientific Research on Innovative Areas [J.K.]; grant from the Leading-edge Research Infrastructure Program [to J.K., H.K.]); from the Young Researcher Overseas Visits Program for Vitalizing Brain Circulation (Japan Society for the Promotion of Science, J.K., H.K., Y.K.); for Japan Society for the Promotion of Science Fellows (Y.K., T.A., N.S.); from the Ministry of Health and Welfare of Japan (J.K., H.K.); from the Global Center of Excellence Program of the Center of Education and Research for Advanced Genome-based Medicine (H.K.); from the Program for Promotion of Basic and Applied Research for Innovations in Bio-oriented Industry (to J.K.); and Kowa Life Science Foundation (J.K.); Kishimoto Foundation Research Grant (J.K.); and from the Yakult Bioscience Foundation (J.K.).
PY - 2014/4/17
Y1 - 2014/4/17
N2 - Mast cells (MCs) mature locally, thus possessing tissue-dependent phenotypes for their critical roles in both protective immunity against pathogens and the development of allergy or inflammation. We previously reported that MCs highly express P2X7, a receptor for extracellular ATP, in the colon but not in the skin. The ATP-P2X7 pathway induces MC activation and consequently exacerbates the inflammation. Here, we identified the mechanisms by which P2X7 expression on MCs is reduced by fibroblasts in the skin, but not in the other tissues. The retinoic-acid-degrading enzyme Cyp26b1 is highly expressed in skin fibroblasts, and its inhibition resulted in the upregulation of P2X7 on MCs. We also noted the increased expression of P2X7 on skin MCs and consequent P2X7- and MC-dependent dermatitis (so-called retinoid dermatitis) in the presence of excessive amounts of retinoic acid. These results demonstrate a unique skin-barrier homeostatic network operating through Cyp26b1-mediated inhibition of ATP-dependent MC activation by fibroblasts.
AB - Mast cells (MCs) mature locally, thus possessing tissue-dependent phenotypes for their critical roles in both protective immunity against pathogens and the development of allergy or inflammation. We previously reported that MCs highly express P2X7, a receptor for extracellular ATP, in the colon but not in the skin. The ATP-P2X7 pathway induces MC activation and consequently exacerbates the inflammation. Here, we identified the mechanisms by which P2X7 expression on MCs is reduced by fibroblasts in the skin, but not in the other tissues. The retinoic-acid-degrading enzyme Cyp26b1 is highly expressed in skin fibroblasts, and its inhibition resulted in the upregulation of P2X7 on MCs. We also noted the increased expression of P2X7 on skin MCs and consequent P2X7- and MC-dependent dermatitis (so-called retinoid dermatitis) in the presence of excessive amounts of retinoic acid. These results demonstrate a unique skin-barrier homeostatic network operating through Cyp26b1-mediated inhibition of ATP-dependent MC activation by fibroblasts.
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U2 - 10.1016/j.immuni.2014.01.014
DO - 10.1016/j.immuni.2014.01.014
M3 - Article
C2 - 24726878
AN - SCOPUS:84899071187
VL - 40
SP - 530
EP - 541
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 4
ER -