Immune Modulatory Effects of IL-22 On Allergen-Induced Pulmonary Inflammation

Abstract

IL-22 is a Th17/Th22 cytokine that is increased in asthma. However, recent animal studies showed controversial findings in the effects of IL-22 in allergic asthma. To determine the role of IL-22 in ovalbumin-induced allergic inflammation we generated inducible lung-specific IL-22 transgenic mice. Transgenic IL-22 expression and signaling activity in the lung were determined. Ovalbumin (OVA)-induced pulmonary inflammation, immune responses, and airway hyperresponsiveness (AHR) were examined and compared between IL-22 transgenic mice and wild type controls. Following doxycycline (Dox) induction, IL-22 protein was readily detected in the large (CC10 promoter) and small (SPC promoter) airway epithelial cells. IL-22 signaling was evidenced by phosphorylated STAT3. After OVA sensitization and challenge, compared to wild type littermates, IL-22 transgenic mice showed decreased eosinophils in the bronchoalveolar lavage (BAL), and in lung tissue, decreased mucus metaplasia in the airways, and reduced AHR. Among the cytokines and chemokines examined, IL-13 levels were reduced in the BAL fluid as well as in lymphocytes from local draining lymph nodes of IL-22 transgenic mice. No effect was seen on the levels of serum total or OVA-specific IgE or IgG. These findings indicate that IL-22 has immune modulatory effects on pulmonary inflammatory responses in allergen-induced asthma.

Role of Th22 and IL-22 in pathogenesis of allergic airway diseases: Pro-inflammatory or anti-inflammatory effect?

“…YBronchial hypersensitivity Taube et al, 2011 [22] Fang et al, 2014 [21] Besnard et al, 2011 [18] In vivo, with mice challenged with ovalbumin In vivo, with mice challenged with ovalbumin In vivo, with mice challenged with ovalbumin (after addition of exogenous recombinant IL-22 during the antigen challenge) YIL- 33 YInduction of the differentiation of IL-5+ IL-4À CD4+ Th cells Y YEosinophilic inflammation Besnard et al, 2011 [18] In vivo, with mice challenged with ovalbumin (after addition of exogenous recombinant IL-22 during the antigen challenge)…”

“…Recent studies involving experimental animal models have shown results contradicting those reported previously; Th22 and IL-22 have an anti-inflammatory effect in airway inflammation. 21,22 Some studies using animals reported that IL-22-positive mice had a reduced number of eosinophils and a lower level of IL-13 (which usually increases bronchial hypersensitivity) in the bronchoalveolar lavage and mucus-producing cells in the airways after ovalbumin stimulation when compared with IL-22-negative mice. 21,22,38 Moreover, an in vitro study with bronchial epithelial cells from healthy and asthmatic subjects revealed that IL-22 might inhibit the IFN-gamma-induced expression of CD54 (intercellular adhesion molecule 1, which plays an important role in T cell migration and recruitment), and chemokines CCL5 (chemoattractant for eosinophils, T lymphocytes, and monocytes) and CXCL10 (important for the recruitment of lymphocytes).…”

Novel innate and adaptive lymphocytes: The new players in the pathogenesis of inflammatory upper airway diseases

“…Some evidence suggests that IL-22 acts as a proinflammatory cytokine, but others pointed to an opposite function. 66,67 These discrepancies may be due to the difference in the study methods and the time-points to block or exaggerate IL-22 expression in murine models. 66,67 For example, allergic lung inflam- Dermatophagoides pteronyssinus and Dermatophagoides farinae.…”

“…66,67 These discrepancies may be due to the difference in the study methods and the time-points to block or exaggerate IL-22 expression in murine models. 66,67 For example, allergic lung inflam- Dermatophagoides pteronyssinus and Dermatophagoides farinae. 73 However, whether up-regulated IL-22 has a pathogenic role or functions as a negative feedback mechanism to control inflammation in AR requires future investigations.…”

“…mation was drastically inhibited by IL-22 neutralization during immunization, but exaggerated by IL-22 neutralization during challenge in wild-type mice 66. Based on the data generated from IL-22-transgenic mice with IL-22 overexpression specifically in lungs, IL-22 was found to function as a negative regulator of allergen-induced airway hypersensitivity reaction 67. The inhibitory effect of IL-22 on allergic pulmonary inflammation may partially associate with its function to reduce antigen uptake by DCs and expression of costimulatory molecules on DCs 68.…”