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Review
. 2017 Feb 2:4:3.
doi: 10.1186/s40779-017-0115-8. eCollection 2017.

Role of the IL-33-ST2 axis in sepsis

Hui Xu  1   2 , Heth R Turnquist  1   3 , Rosemary Hoffman  1   2 , Timothy R Billiar  1
Affiliations
Review

Role of the IL-33-ST2 axis in sepsis

Hui Xu et al. Mil Med Res. .

Abstract

Sepsis remains a major clinical problem with high morbidity and mortality. As new inflammatory mediators are characterized, it is important to understand their roles in sepsis. Interleukin 33 (IL-33) is a recently described member of the IL-1 family that is widely expressed in cells of barrier tissues. Upon tissue damage, IL-33 is released as an alarmin and activates various types of cells of both the innate and adaptive immune system through binding to the ST2/IL-1 receptor accessory protein complex. IL-33 has apparent pleiotropic functions in many disease models, with its actions strongly shaped by the local microenvironment. Recent studies have established a role for the IL-33-ST2 axis in the initiation and perpetuation of inflammation during endotoxemia, but its roles in sepsis appear to be organism and model dependent. In this review, we focus on the recent advances in understanding the role of the IL-33/ST2 axis in sepsis.

Keywords: ST2; Sepsis, Interleukin-33.

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Figures

Fig. 1
Fig. 1
Cellular sources and cellular targets of IL-33. IL-33 is released from endothelial cells, epithelial cells and fibroblasts in response to tissue damage and/or mechanical stress (indicated as dotted arrow). After release, IL-33 functions as an alarmin and activates various types of cells (indicated as solid arrow), including Th2 cells, Tregs, basophils, mast cells, eosinophils, macrophages, dendritic cells, innate lymphoid cells (ILC2s), NK cells and NKT cells. These cells respond to IL-33/ST2 signaling by producing both pro-inflammatory and anti-inflammatory mediators depending on the immune context in different tissues and diseases
Fig. 2
Fig. 2
IL-33/ST2 signaling. The binding of IL-33 to ST2 results in the activation of IL-33 bioactivities via intracellular pathways, while sST2 acts as a decoy receptor for IL-33
See this image and copyright information in PMC

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