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Interleukin (IL)-33 is a new member of the IL-1 superfamily of cytokines that is expressed by mainly stromal cells, such as epithelial and endothelial cells, and its expression is upregulated following pro-inflammatory stimulation. IL-33 can function both as a traditional cytokine and as a nuclear factor regulating gene transcription. It is thought to function as an 'alarmin' released following cell necrosis to alerting the immune system to tissue damage or stress. It mediates its biological effects via interaction with the receptors ST2 (IL-1RL1) and IL-1 receptor accessory protein (IL-1RAcP), both of which are widely expressed, particularly by innate immune cells and T helper 2 (Th2) cells. IL-33 strongly induces Th2 cytokine production from these cells and can promote the pathogenesis of Th2-related disease such as asthma, atopic dermatitis and anaphylaxis. However, IL-33 has shown various protective effects in cardiovascular diseases such as atherosclerosis, obesity, type 2 diabetes and cardiac remodeling. Thus, the effects of IL-33 are either pro- or anti-inflammatory depending on the disease and the model
Source: Miler, A. (2011).
Role of IL-33 in inflammation and disease
IL-33 is a member of the IL-1 family of cytokines that includes IL-1α, IL-1β and IL-18. In contrast to other IL-1 related cytokines, except for IL-1α, IL-33 is primarily localized in the nucleus and it associates with chromatin where it can bind to the surface of nucleosomes and affect chromatin remodeling [94] and [95]. It is crucial for the induction of Th2 type cytokine-associated immune responses and thus has been extensively studied in the context of allergic disease where it has proinflammatory effects and in helminth infections where it is protective [96]. In models of anaphylaxis IL-33 directly induces mast cell degranulation after IgE sensitization. There appears to be an autocrine inflammatory loop induced by IL-33 in mast cells. IL-33 is produced by murine mast cells and mast cells also constitutively express ST2, a receptor subunit that together with IL-1 receptor accessory protein (IL-1RAcP) makes up the heterodimeric IL-33 receptor. Notably, similar to IL-3 and SCF, IL-33 can also directly induce cytokine and chemokine secretion from mast cells without affecting degranulation [94] and [95]. The proinflammatory activities of IL-33 and its link to mast cells make it a good candidate for studies in mast cell-dependent inflammatory autoimmune diseases.
Source: Walker et al (2012).
New insights into the role of mast cells in autoimmunity: Evidence for a common mechanism of action?
We provide evidences of a specific role for IL-33 receptor signaling in nitric oxide induction through local IFN-γ modulation, suggesting that nitric oxide overproduction might have an important role in the progression of experimental viral encephalitis.
Source: Franca et al (2016).
IL-33 signaling is essential to attenuate viral-induced encephalitis development by downregulating iNOS expression in the central nervous system.
@Jonathan Edwards have you seen this paper?