Mast Cells May Regulate The Anti-Inflammatory Activity of IL-37.

Theoharis C Theoharides,Irene Tsilioni,Pio Conti

doi:10.3390/ijms20153701

Theoharis C Theoharides, Irene Tsilioni + Show 1 more

Open Access

https://doi.org/10.3390/ijms20153701

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Abstract

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.

Highlights

Mast cells derive from bone marrow progenitors and mature perivascularly in all tissues [1], where they are involved in allergic reactions [2]
Mast cells are stimulated by pathogens [4], drugs, foods, heavy metals, and “danger signals” [2], as well as certain neuropeptides including corticotropin-releasing hormone (CRH) [5], neurotensin (NT) [6] and substance P (SP) [7,8]
Stimulated mast cells can secrete numerous bioactive mediators [15,16,17], utilizing different secretory pathways [18]. Some of these mediators are prestored in secretory granules such as histamine, tryptase and tumor necrosis factor (TNF) [19,20]; others are synthesized de novo and include leukotrienes, prostaglandins, chemokines (CCXL8, CCL2) and cytokines [20,21], that include pro- and anti-inflammatory members, [22]

Summary

Mast Cells in Inflammation

Mast cells derive from bone marrow progenitors and mature perivascularly in all tissues [1], where they are involved in allergic reactions [2]. Mast cells are stimulated by pathogens [4], drugs, foods, heavy metals, and “danger signals” [2], as well as certain neuropeptides including corticotropin-releasing hormone (CRH) [5], neurotensin (NT) [6] and substance P (SP) [7,8]. Both NT [9,10] and SP [11,12,13,14] are known to participate in inflammatory processes. Mast cells are critical for allergic reactions [2,24], but are important in innate and acquired immunity [25,26], antigen presentation [27,28] and inflammation [29,30]

IL-37 as An Anti-Inflammatory Agent

Mast Cell-Derived Heparin and Tryptase May Regulate IL-37