IL-33 is a nuclear cytokine from the IL-1 family constitutively expressed in epithelial barrier tissues and lymphoid organs, which plays important roles in type-2 innate immunity and human asthma.
IL-33 is likely to play a critical role in asthma because the IL33 and ST2/IL1RL1 genes have been reproducibly identified as major susceptibility loci in large-scale genome-wide association studies.
For ORMDL3-GSDMB region, rs8067378 (G allele protective against asthma) was correlated with decreased expression of GSDMB in BEC and BAL (P = 1.3 × 10(-4) and 0.04) but not ORMDL3. rs992969 in the promoter region of IL33 (A allele associated with higher eosinophil counts and risk for asthma) was correlated with increased expression of IL33 in BEC (P = 1.3 × 10(-6) ) but not in BAL.
Both reduced (active) and disulphide bonded (inactive) forms of IL-33 can be detected in lung lavage samples from mice challenged with Alternaria extract and in sputum from patients with moderate-severe asthma.
The level of IL-33 mRNA expression was significantly higher in patients with asthma compared to healthy individuals (Median (IQR) 1.12 (0.78) vs. 0.86, P = 0.04).
Further work is required to develop human monoclonal antibodies (hMabs) directed against IL-25 and IL-33 or their receptors, to help understand their role in the initiation and/or persistence of asthma.
Also, human ILC2s and Treg cells were adoptively transferred into NOD SCID γC-deficient mice, which were given isotype or anti-inducible T-cell costimulator ligand (ICOSL) antibodies and then challenged with IL-33 and assessed for airway hyperreactivity.
Plasma IL-25, IL-33, and TSLP levels were measured before and after aspirin challenge in subjects with AERD (n = 25) and aspirin-tolerant asthma (ATA, n = 25) by enzyme-linked immunosorbent assay (ELISA).
TLR expression by circulating HPC and interleukin (IL)-25 (IL-17RB), IL-33 (ST2) and thymic stromal lymphopoietin receptor (TSLPR) expression after TLR ligation were examined by flow cytometry at baseline and, in asthmatics, following allergen challenge.
Treatment with antibiotics associated with reduced ST2 in blood cells of both asthmatic and control children and reduced IL-33 levels in the airways of asthmatic children.
We tested for possible associations between SNPs in the IL33 and ST2 with asthma and allergy markers such as specific IgE (sIgE), IL-5 and IL-13 production and skin prick test (SPT).
Together these data demonstrate that rs146597587-C is a loss of function mutation and support the hypothesis that IL-33 haploinsufficiency protects against asthma.
Particulate matter impaired epithelium signalling (TSLP, IL-33 and CXCL8) in saHBEC co-cultures despite C-C chemokine ligand 2 induction.Crosstalk between HBEC and moDC can be established <i>in vitro</i>, driving a T1-type response with cHBEC and a T2-type response with saHBEC.