Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan; Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Osaka 567-0085, Japan.
Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0075, Japan; Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Osaka 567-0085, Japan; Department of Medical Genome Science, Graduate School of Frontier Science, The University of Tokyo, Chiba 277-8561, Japan.
Immunity. 2014 Apr 17;40(4):530-41. doi: 10.1016/j.immuni.2014.01.014. Epub 2014 Apr 10.
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.
肥大细胞 (MCs) 在局部成熟，因此在其对抗病原体的保护性免疫和过敏或炎症发展中的关键作用方面具有组织依赖性表型。我们之前曾报道过，MCs 在结肠中高度表达 P2X7，即细胞外 ATP 的受体，但在皮肤中不表达。ATP-P2X7 途径诱导 MC 激活，进而加重炎症。在这里，我们确定了皮肤成纤维细胞而非其他组织中降低 MC 上 P2X7 表达的机制。维甲酸降解酶 Cyp26b1 在皮肤成纤维细胞中高度表达，其抑制导致 MC 上 P2X7 的上调。我们还注意到在存在过量维甲酸的情况下，皮肤 MC 上 P2X7 的表达增加，以及随后的 P2X7 和 MC 依赖性皮炎（所谓的维甲酸皮炎）。这些结果表明，通过 Cyp26b1 介导的成纤维细胞对 ATP 依赖性 MC 激活的抑制作用，存在一个独特的皮肤屏障稳态网络。
