Immune modulatory effects of IL-22 on allergen-induced pulmonary inflammation.

Ping Fang,Zhou Zhu,Tao Zheng,Yuqi Zhou,Li Zhou,Jay K Kolls

doi:10.1371/journal.pone.0107454

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.

Highlights

Allergen-induced pulmonary responses in asthma are characterized by eosinophil infiltration, mucus hypersecretion, airway hyperreactivity and bronchoconstriction
After Dox induction for 4 weeks, IL-22 mRNA was readily detected in the lung tissue and IL-22 protein was elevated in the bronchoalveolar lavage (BAL) fluid of Tg(+) mice but not in Tg(2) mice by ELISA (Figure 1A, 1B)
Recent studies suggested that Th17/ Th22 cytokines IL-17 and IL-22 have regulatory effects on allergic airway inflammation

Summary

Introduction

Allergen-induced pulmonary responses in asthma are characterized by eosinophil infiltration, mucus hypersecretion, airway hyperreactivity and bronchoconstriction. The Th17 cytokine IL-17A is critical in the pathogenesis of severe asthma [4,5]. A novel Th17/Th22 cytokine, IL22, was found to have immune modulatory effects on pulmonary allergic inflammation [6,7,8]. Th17/Th22 cells mainly secrete IL-17A, IL-17F and IL-22 [9,10] Both IL-17 and IL-22 have been found to have a major impact in epithelial cells in various tissues and are key regulators of homeostasis and epithelial barrier function. The immune modulatory effects of IL-22 in allergen-induced lung inflammation are not well understood

Methods

Results

Conclusion