Decoding asthma: Translating genetic variation in IL33 and IL1RL1 into disease pathophysiology

Perinatal Activation of the Interleukin-33 Pathway Promotes Type 2 Immunity in the Developing Lung

“…Consistently, polymorphisms in IL1RL1, coding for ST2 (IL-33R), as well as the IL33 gene itself have been found associated with asthma and blood eosinophil counts, particularly in childhood asthma (Bøn-nelykke et al, 2014;Castanhinha et al, 2015;Gordon et al, 2016;Moffatt et al, 2010;Saglani et al, 2013;Savenije et al, 2011;Torgerson et al, 2011;Traister et al, 2015). In asthmatics, polymorphisms in IL1RL1 also control the relative abundance of the cell-bound IL-33R (ST2L) versus the soluble IL-33 receptor (sST2), that acts as a decoy receptor and antagonist of the IL-33-IL-33R axis (Grotenboer et al, 2013;Traister et al, 2015). It would be interesting to now analyze whether carriers of the IL33 and IL1RL1 risk alleles are at increased risk to specifically develop allergic asthma at young age, and whether SNPs associated with high expression of sST2 are associated with protection.…”

Immunochip Identifies Novel, and Replicates Known, Genetic Risk Loci for Rheumatoid Arthritis in Black South Africans

“…This receptor interacts with molecules such as MyD88, IRAK1, IRAK4 and TRAF6. Variants of this gene have been associated with asthma (39) and with severe hand osteoarthritis (40). Numerous significantly associated SNPs locate to the IRF1 gene on chromosome 5, which is responsible for the activation of interferon α and β. Knockout mice with deletion of IRF1 had abnormal peripheral blood lymphocytes, specifically decreased CD8…”

IL-33 and Thymic Stromal Lymphopoietin in mast cell functions

“…Most of the asthma-associated SNPs are located in the promoter region or 5′ region of IL33, potentially allowing a role in the regulation of IL33 expression (Grotenboer et al, 2013), but more functional study of these SNPs is required to verify this hypothesis. Providing additional evidence for the role of the IL-33 pathway in allergic disease is the fact that also the gene encoding its receptor ST2 (IL1RL1) has been associated with several allergic disorders (Li et al, 2015), including asthma (Moffatt et al, 2010;Ramasamy et al, 2012;Torgerson et al, 2011;Wan et al, 2012), atopic dermatitis (Hirota et al, 2012) and allergic rhinitis (Bonnelykke et al, 2013), but also an association of IL1RL1 exists with allergic sensitization in general (Bonnelykke et al, 2013) and with eosinophil count in peripheral blood (Gudbjartsson et al, 2009).…”