In an experimental model of fungal-associated allergic airway inflammation, we demonstrate that IL-1R1 signaling promotes type 1 (IFN-γ, CXCL9, CXCL10) and type 17 (IL-17A, IL-22) responses that were associated with neutrophilic inflammation and increased airway hyperreactivity.
In accordance with the fact that lung epithelial cells play a critical role in the pathogenesis of asthma, we and other groups have shown that IL-22 is involved in the regulation of allergic airway inflammation.
Here, we review the current understanding of the molecular and cellular mechanisms underlying IL-22-mediated regulation of airway inflammation in asthma.
Employing IL22<sup>Cre</sup>R26R<sup>eYFP</sup> reporter mice, we identified γδ T cells, iNKT cells, CD4 T cells and ILC3s as sources of IL-22 during fungal asthma; however, only iNKT cells were significantly increased after IL-7 administration.
Peripheral blood neutrophils isolated from asthmatics were stimulated with IL-21, IL-23, and IL-6 cytokines and their ability to produce IL-17A and IL-17F was determined relative to healthy controls.
Our data suggest that miR-323-3p acts in a negative feedback loop to control the production of IL-22 in IL-22/IL-17-producing T cells and might thus impact the T-cell responses in asthma.
Cytokine-producing Th subsets including Th1 (IFN-γ), Th2 (IL-4, IL-5, IL-13), Th9 (IL-9), Th17 (IL-17), Th22 (IL-22), and T regulatory (IL-10) cells have all been suggested to play a role in the development of asthma.
Recent studies clearly show that not only Th2 cytokines but also other T cell-related cytokines such as IL-17A and IL-22 as well as epithelial cell cytokines such as IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) are involved in the pathogenesis of asthma.
The promotion of protein S-glutathionylation by asthma mediators such as interleukin-22 and platelet-derived growth factor or by knocking down glutaredoxin-1 or thioredoxin activated cell growth signaling.
Chronic diseases such as asthma and chronic obstructive pulmonary disease have been associated with IL-17 and IL-22 responses directed against innocuous antigens.
We sought to investigate the production of the TH17-associated cytokines IL-17A and IL-22 in culture in patients with moderate-to-severe asthma defined on the basis of their clinical response to steroids and the susceptibility of this response to inhibition by steroids and the active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25[OH]2D3).
To identify the most vulnerable population among those children we selected asthma as a typical allergy-related disease, and could show that there are significant differences in the levels of IL-22 mRNA expression between IgE negative non-asthmatic subject and asthmatic children showing positive IgE reaction toward egg or milk, again.
The plasma concentrations of IL-22 had negative correlation with the predicted percentage of forced expiratory volume in the first second (FEV1%) and the percentage of FEV1 and forced vital capacity (FEV1/FVC%) and it was positively correlated with the asthma severity score (ASS) of the asthmatics.