Interleukin-22 in human allergy and asthma

Abstract

Interleukin 22 (IL-22) is а newly-described Т helper cytokine which has been implicated in tissue regenerative processes in the gut and skin. Allergic asthma results from exposure to otherwise harmless environmental inhaled allergens that trigger Th2 Т Iymphocyte-driven IgE-аssосiаtеd immune responses in atopic individuals that contribute to airway inflammation and reversible airflow obstruction. In the long-term, this aberrant immune response is believed to increase in complexity and contribute to the permanent changes in the airways, including tissue remodelling and associated irreversible airway obstruction. In view of the known effects of IL-22 in wound healing, the overall aim of this research was to establish whether IL-22 is present in allergy and allergic asthma and to understand the influence of IL-22 on structural cells of the airway, with particular emphasis оп tissue remodelling. We, therefore, explored the presence of IL-22 and its receptors during allergen-induced late responses in the bronchi and skin and measured IL-22 production and its regulation in peripheral blood mononuclear cells (PBMCs), Т cell lines and clones derived from asthmatic bronchial muсоsa. IL-22 was increased in bгonchoalveolaг lavage after allergen inhalation in asthmatics but not in control subjects. While we were unable to reliably immunostain IL-22, its receptors were present within the cutaneous connective tissue and co-Iocalised with HSP-47, а marker of early fibrobIasts. In PBMCs, IL-22 increased after allergen stimulation whereas there was nо difference between atopics and control subjects. In Т cell lines derived from asthmatic bronchial mucosa, IL-22 was mainly found in СD4+ Т helper cells of Th1 and Th22 origin. IL-22 receptors were expressed by cultured bronchial epithelial cells, smooth muscle cells and pulmonary fibroblasts and were increased in expression in the presence of interferon-γ (IFN-γ). IL-22 was able to accelerate wound closure of bronchial epithelial cells independent of effects on cellular proliferation. Thus, IL-22 appears to be а Th1-related cytokine that may have а dual role in airway inflammation and repair.