Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA.
Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA.
Int J Mol Sci. 2019 Jul 29;20(15):3701. doi: 10.3390/ijms20153701.
Mast cells are unique immune cells involved in allergic reactions, but also in immunity and inflammation. Interleukin 37 (IL-37) has emerged as an important regulatory cytokine with ability to inhibit immune and inflammatory processes. IL-37 is made primarily by macrophages upon activation of toll-like receptors (TLR) leading to generation of mature IL-37 via the action of caspase 1. In this review, we advance the premise that mast cells could regulate the anti-inflammatory activity of the IL-37 via their secretion of heparin and tryptase. Extracellular IL-37 could either dimerize in the presence of heparin and lose biological activity, or be acted upon by proteases that can generate even more biologically active IL-37 forms. Molecules that could selectively inhibit the secretion of mast cell mediators may, therefore, be used together with IL-37 as novel therapeutic agents.
肥大细胞是一种独特的免疫细胞，参与过敏反应，但也参与免疫和炎症反应。白细胞介素 37（IL-37）作为一种重要的调节性细胞因子，具有抑制免疫和炎症过程的能力。IL-37 主要由巨噬细胞在激活 Toll 样受体（TLR）后产生，通过半胱天冬酶 1 的作用产生成熟的 IL-37。在这篇综述中，我们提出假设，即肥大细胞可以通过其肝素和胰蛋白酶的分泌来调节 IL-37 的抗炎活性。细胞外的 IL-37 可以在肝素存在的情况下二聚化并失去生物活性，或者被蛋白酶作用，从而产生更具生物活性的 IL-37 形式。因此，能够选择性抑制肥大细胞介质分泌的分子可以与 IL-37 一起用作新型治疗剂。
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