Mast Cells May Regulate The Anti-Inflammatory Activity of IL-37
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
Department of Internal Medicine, Tufts University School of Medicine and Tufts Medical Center, Boston, MA 02111, USA
Immunology Division, Postgraduate Medical School, University of Chieti, 65100 Pescara, Italy
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(15), 3701; https://doi.org/10.3390/ijms20153701
Received: 6 June 2019 / Revised: 13 July 2019 / Accepted: 19 July 2019 / Published: 29 July 2019
(This article belongs to the Special Issue Mast Cells in Health and Disease)
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.