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Interleukin-33 (IL-33) was originally discovered as a potent inducer of type 2 immune responses. Since then, IL-33 has been demonstrated to have pleiotropic immunomodulatory functions and has been implicated in many immune-mediated diseases including infection, allergy, and various autoimmune and inflammatory ...

Interleukin-33 (IL-33) was originally discovered as a potent inducer of type 2 immune responses. Since then, IL-33 has been demonstrated to have pleiotropic immunomodulatory functions and has been implicated in many immune-mediated diseases including infection, allergy, and various autoimmune and inflammatory disorders. Increasing evidence indicates that the actions of IL-33 in the immune system are regulated by a wide range of innate and adaptive immune cells including dendritic cells, mast cells, macrophages, Th1 cells, Th2 cells, CD8+ T cells, T regulatory cells, NK cells and group 2 innate lymphoid cells.

Recent reports however have unravelled the multifaceted roles of IL-33 in (i) tissue development, (ii) metabolic homeostasis, and (iii) the pathogenesis of diseases beyond immune regulation. IL-33 and/or its receptor ST2 are highly expressed in epithelial and endothelial cells, as well as in many organ-specific cells, e.g. glial cells in the eye and nervous system, and in fibroblasts located in the joint and lung. Upon tissue stress or damage, IL-33 is released and acts as an alarmin, and IL-33/ST2 pathway exhibits organ-specific functions under pathophysiological conditions in the skin, eye, lung, joint, gut, nervous system and cardiovascular system and in cancer development. With immunity and inflammation often playing critical roles in pathological progression, IL-33 is therefore emerging as one of the key players in tissue-immune crosstalk through its interaction with both immune and organ-specific cells. Further advances in our understanding of the actions of IL-33 in the complex dynamic interactions between immune and non-immune cells will help to elucidate the contribution of IL-33/ST2 axis in health and disease.

This Research Topic aims to provide a forum for presenting novel and important findings on IL-33. We welcome the submission of Reviews, Mini-Reviews and Original Research articles covering, but not limited to, the following topics:

1. The molecular and cellular characteristics of IL-33 as a traditional extracellular cytokine as well as a nuclear transcription factor.
2. The function of IL-33/ST2 signaling pathway in tissue development and homeostasis.
3. The roles of IL-33 in disease progression and the underlying mechanisms of their actions through modulating immune and organ-specific tissue cells in infection, inflammation, autoimmunity, cancer, injury, vascular and neurological diseases.

Keywords: IL-33


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