Volume 13 Supplement 2

Kitasato Symposium 2011: Translational prospects for cytokines in 2011

Open Access

Interleukin-37 as fundamental inhibitor of innate immunity

  • P Bufler1
Arthritis Research & Therapy201113(Suppl 2):O15

DOI: 10.1186/ar3419

Published: 16 September 2011

The interleukin-1 (IL-1) family of ligands has 11 members of which most are proinflammatory. The receptors, signaling pathways, and functions of the classical family members (IL-1α, IL-1β and IL-18) have been studied extensively. However, knowledge of Interleukin-37 (IL-37/IL-1F7), which was first identified by in silico research in 2000 remains limited.

IL-37 shares critical amino acid residues with IL-18 and binds to the IL-18-binding protein enhancing its ability to inhibit IL-18-induced interferon-γ. Data suggest that IL-37 also binds to the IL-18Rα and, for its anti-inflammatory properties, likely recruits an accessory receptor chain with inhibitory properties, such as the single Ig IL-1 related receptor. We recently reported that overexpression of IL-37 in cells of monocytic or epithelial origin almost completely abolishes the production of proinflammatory cytokines as IL-1α/β, TNFα, IL-6 and IL-8 in response to TLR-ligands or IL-1β. Anti-inflammatory cytokines were unaffected. Vice versa, functional knockdown of IL-37 in primary human cells by siRNA increased the production of proinflammatory cytokines. IL-37tg mice are protected against LPS-induced shock. Thus IL-37 is a fundamental inhibitor of innate immune responses.

IL-37 protein is expressed in human monocytes and upregulated by LPS. Similarly to IL-1α and IL-33, IL-37 is expressed intracellularly and translocates to the nucleus upon cell stimulation in a caspase-1 dependent manner. IL-37 interacts inside the cell with Smad3 and inflammation in IL-37tg mice is increased when endogenous Smad3 is depleted. IL-37 is also secreted in the supernatant of stimulated transfected cells or peripheral mononuclear blood cells. However, the extracellular functionality of IL-37 is still elusive.

Authors’ Affiliations

(1)
Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University

Copyright

© BioMed Central Ltd 2011

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Advertisement