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, 11 (4), 54-64

The Role of Interleukin-37 in the Pathogenesis of Allergic Diseases

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The Role of Interleukin-37 in the Pathogenesis of Allergic Diseases

I P Shilovskiy et al. Acta Naturae.

Abstract

Cytokines of the interleukin-1 (IL-1) family play an important role in the realization of the protective functions of innate immunity and are the key mediators involved in the pathogenesis of a wide range of diseases, including various manifestations of allergy. The IL-1 family includes more than 11 members. However, the functions of many of them remain to be elucidated. Recently, new members of the IL-1 family have been discovered. In 2000, several independent research groups reported the discovery of a new interleukin of this family, which was named IL-37, or IL-1F7 (according to the new nomenclature). IL-37 was assigned to the IL-1 family based on its structural similarity with other members of this family. The study of its biological properties showed that its activity changes in inflammatory diseases, such as rheumatoid arthritis, psoriasis, as well as allergic diseases (allergic rhinitis, bronchial asthma, and atopic dermatitis). However, unlike most members of the IL-1 family, IL-37 acts as a negative regulator of inflammation. Activation of IL-37 suppresses inflammation, resulting in the suppression of inflammatory cytokines and chemokines, which in turn prevents infiltration of pro-inflammatory cells, mainly eosinophils and neutrophils. The exact molecular and cellular mechanisms of the anti-inflammatory effect of IL-37 in the development of allergic diseases (AD) have not been fully studied. This review summarizes and analyzes the accumulated experimental data on the role of IL-37 in the pathogenesis of AD, such as allergic rhinitis, bronchial asthma, and atopic dermatitis.

Keywords: IL-37; anti-inflammatory cytokines; bronchial asthma; gene expression; pro-inflammatory cytokines.

Figures

Fig. 1
Fig. 1
The structure of the gene IL-37 and its five alternative transcripts
Fig. 2
Fig. 2
Mechanisms of the anti-inflammatory effects of IL-37. IL-18 exerts its pro-inflammatory effects through a receptor complex consisting of the IL-18Rα and IL-18Rβ chains. The TIR domains come together and further bind to the MyD88 factor inducing the pro-inflammatory effect. IL-37 is synthesized as a precursor (pre-IL-37) which is capable of secreting into the extracellular space, where it is processed to a mature form through an unidentified mechanism. Mature IL-37 binds to the chains IL-18Rα and IL-1R8 (instead of IL-18Rβ); at the same time, the IL-1R8 chain carries the mutant TIRb domain (instead of functional TIR), which does not allow realization of the MyD88-mediated inflammatory effect [21].The precursor of IL-37 is also capable of being processed intracellularly into mature form by Caspase-1. In the cytosol, IL-37 binds to the phosphorylated form of the Smad3 factor (pSmad3). Apparently, The IL-37 / Smad3 complex is able to translocate into the nucleus and inhibit the transcription of pro-inflammatory genes (the ability of the complex to bind to DNA has not been confirmed yet)

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