High Expression of IL-22 Suppresses Antigen-Induced Immune Responses and Eosinophilic Airway Inflammation via an IL-10–Associated Mechanism

Abstract

Allergic inflammation in the airway is generally considered a Th2-type immune response. However, Th17-type immune responses also play important roles in this process, especially in the pathogenesis of severe asthma. IL-22 is a Th17-type cytokine and thus might play roles in the development of allergic airway inflammation. There is increasing evidence that IL-22 can act as a proinflammatory or anti-inflammatory cytokine depending on the inflammatory context. However, its role in Ag-induced immune responses is not well understood. This study examined whether IL-22 could suppress allergic airway inflammation and its mechanism of action. BALB/c mice were sensitized and challenged with OVA-Ag to induce airway inflammation. An IL-22–producing plasmid vector was delivered before the systemic sensitization or immediately before the airway challenge. Delivery of the IL-22 gene before sensitization, but not immediately before challenge, suppressed eosinophilic airway inflammation. IL-22 gene delivery suppressed Ag-induced proliferation and overall cytokine production in CD4+ T cells, indicating that it could suppress Ag-induced T cell priming. Antagonism of IL-22 by IL-22–binding protein abolished IL-22–induced immune suppression, suggesting that IL-22 protein itself played an essential role. IL-22 gene delivery neither increased regulatory T cells nor suppressed dendritic cell functions. The suppression by IL-22 was abolished by deletion of the IL-10 gene or neutralization of the IL-10 protein. Finally, IL-22 gene delivery increased IL-10 production in draining lymph nodes. These findings suggested that IL-22 could have an immunosuppressive effect during the early stage of an immune response. Furthermore, IL-10 plays an important role in the immune suppression by IL-22.

Helper T Cell Plasticity: Impact of Extrinsic and Intrinsic Signals on Transcriptomes and Epigenomes

“…Mutations and polymorphisms of IL-10 or its receptor are associated with inflammatory bowel disease (Glocker et al 2009) (Engelhardt et al 2013). IL-22 is yet another critical cytokine; in certain circumstances, it too has essential anti-inflammatory properties (Nakagome et al 2011). Finally, IL-35 is a regulatory cytokine that is able to generate a population of cells with suppressive activity called Tr35 cells (Collison et al 2007).…”

Enhanced production of IL-17A in patients with severe asthma is inhibited by 1α,25-dihydroxyvitamin D3 in a glucocorticoid-independent fashion

“…In addition to IL-17A, IL-22 is commonly produced by Th17 cells. In various animal models of disease IL-22 can elicit damaging or protective responses possibly dependent on the location, cellular sources, cytokine milieu and timing of its expression (24)(25)(26).…”

Interleukin-22 Reduces Lung Inflammation during Influenza A Virus Infection and Protects against Secondary Bacterial Infection

“…IL-22 has been shown to attenuate antigen (Ag)-induced pulmonary immune responses in some settings (23,(25)(26)(27). We thus compared the virus-specific CD8 ϩ T cell response in IAV-infected WT and Il22 Ϫ/Ϫ mice in terms of cell number and cytokine production.…”

“…In the lungs, IL-22 protects against experimental lung fibrosis (23) and ventilator-induced lung injury (24). IL-22 also limits Th2-mediated airway inflammation and tissue damage during asthma (25)(26)(27). On the other hand, uncontrolled IL-22 production favors dermal inflammation and acanthosis, bleomycin-induced airway inflammation, collagen-induced arthritis, and lipopolysaccharide shock, in part by enhancing tissue inflammation in concert with inflammatory factors such as tumor necrosis factor alpha (TNF-␣) and IL-17 (4,(28)(29)(30)(31).…”