IL-33 induces histidine decarboxylase, especially in c-kit+ cells and mast cells, and roles of histamine include negative regulation of IL-33-induced eosinophilia
IL-33 induces histidine decarboxylase, especially in c-kit+ cells and mast cells, and roles of histamine include negative regulation of IL-33-induced eosinophilia
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DOI：
10.1007/s00011-023-01699-y
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发表时间：
2023-02-01
影响因子：
6.7
通讯作者：
Endo，Yasuo
中科院分区：
文献类型：
--
作者：
Bando，Kanan;Tanaka，Yukinori;Endo，Yasuo
目的和方法IL-33 存在于内皮细胞、上皮细胞和成纤维细胞样细胞中，并在细胞损伤时释放。据报道，IL-33 可诱导肥大细胞脱颗粒，并与多种疾病有关，包括过敏性疾病。因此，IL-33 相关疾病似乎与组胺相关疾病重叠。除了肥大细胞释放外，组胺还通过组氨酸脱羧酶 (HDC) 的诱导而新形成。已知一些炎症和/或造血细胞因子（IL-1、IL-3等）可诱导HDC，HDC诱导产生的组胺无需储存即可释放。我们检查了 HDC 和组胺在 IL-33 作用中的参与情况。结果向小鼠单次腹腔注射 IL-33，可在数小时内直接和/或通过其他细胞因子（包括 IL-5）在各种组织中诱导 HDC，特别是在造血器官中。表现出HDC诱导的主要细胞是骨髓中的肥大细胞和c-kit+细胞。 HDC也在非造血器官的非肥大细胞中被诱导。 HDC、组胺和组胺 H4 受体 (H4R) 有助于抑制 IL-33 诱导的嗜酸性粒细胞增多。结论IL-33 直接和间接（通过 IL-5）在各种细胞中诱导 HDC，特别是在 c-kit+ 细胞和成熟肥大细胞中，新形成的组胺通过 H4R 有助于负调节 IL-33 诱导的嗜酸性粒细胞增多。
Objective and methodsIL-33 is present in endothelial, epithelial, and fibroblast-like cells and released upon cell injury. IL-33 reportedly induces mast-cell degranulation and is involved in various diseases, including allergic diseases. So, IL-33-related diseases seem to overlap with histamine-related diseases. In addition to the release from mast cells, histamine is newly formed by the induction of histidine decarboxylase (HDC). Some inflammatory and/or hematopoietic cytokines (IL-1, IL-3, etc.) are known to induce HDC, and the histamine produced by HDC induction is released without storage. We examined the involvement of HDC and histamine in the effects of IL-33.ResultsA single intraperitoneal injection of IL-33 into mice induced HDC directly and/or via other cytokines (including IL-5) within a few hours in various tissues, particularly strongly in hematopoietic organs. The major cells exhibiting HDC-induction were mast cells and c-kit+cells in the bone marrow. HDC was also induced in non-mast cells in non-hematopoietic organs. HDC, histamine, and histamine H4 receptors (H4Rs) contributed to the suppression of IL-33-induced eosinophilia.ConclusionIL-33 directly and indirectly (via IL-5) induces HDC in various cells, particularly potently in c-kit+cells and mature mast cells, and the newly formed histamine contributes to the negative regulation of IL-33-induced eosinophilia via H4Rs.