The role of the IL-33/IL-1RL1 axis in mast cell and basophil activation in allergic disorders.
Saluja, Rohit a,*; Ketelaar, Maria E. b,c; Hawro, Tomasz a; Church, Martin K. a; Maurer, Marcus a,1; Nawijn, Martijn C. b,c,1
[Review] Molecular Immunology. 63(1):80-85, January 2015.

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Highlights:

* SNPs in the IL-33 and IL-1RL1 genes play a crucial role in asthma and allergic diseases.

* The IL-33/IL-1RL1 pathway modulates several functions in mast cells and basophils under physiological and pathological conditions.

* Dysregulated activity of the IL-33/IL-1RL1 pathway could contribute to allergic disorders via altered functioning of mast cells and basophils.

* Targeting the IL-33/IL-1RL1 pathway could form a novel therapeutic approach to treat allergic diseases.

Interleukin-33 (IL-33) is a recently discovered cytokine that belongs to the IL-1 superfamily and acts as an important regulator in several allergic disorders. It is considered to function as an alarmin, or danger cytokine, that is released upon structural cell damage. IL-33 activates several immune cells, including Th2 cells, mast cells and basophils, following its interaction with a cell surface heterodimer consisting of an IL-1 receptor-related protein ST2 (IL-1RL1) and IL-1 receptor accessory protein (IL-1RAcP). This activation leads to the production of a variety of Th2-like cytokines that mediate allergic-type immune responses. Thus, IL-33 appears to be a double-edged sword because, in addition to its important contribution to host defence, it exacerbates allergic responses, such as allergic rhinitis and asthma. A major purported mechanism of IL-33 in allergy is the activation of mast cells to produce a variety of pro-inflammatory cytokines and chemokines. In this review, we summarize the current knowledge regarding the genetics and physiology of IL-33 and IL-1RL1 and its association with different allergic diseases by focusing on its effects on mast cells and basophils.

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