IL-22 regulates inflammatory responses to agricultural dust-induced airway inflammation
- Toxicol Appl Pharmacol. 2022 Jul 1:446:116044. doi: 10.1016/j.taap.2022.116044.
- 1. Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 92521, USA.
- 2. Riverside Community College, Riverside, CA 92521, USA.
- 3. Department of Medical Sciences, College of Allied Health Professions, University of Nebraska Medical Center, Omaha, NE 68198, USA.
- 4. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
- 5. Department of Preprofessional Biology, University of Florida, Gainesville, FL 32603, USA.
- 6. Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 92521, USA; Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, 80521, USA. Electronic address: [email protected].
IL-22 is a unique cytokine that is upregulated in many chronic inflammatory diseases, including asthma, and modulates tissue responses during inflammation. However, the role of IL-22 in the resolution of inflammation and how this contributes to lung repair processes are largely unknown. Here, we tested the hypothesis that IL-22 signaling is critical in inflammation resolution after repetitive exposure to agricultural dust. Using an established mouse model of organic dust extract-induced lung inflammation, we found that IL-22 knockout mice have an enhanced response to agricultural dust as evidenced by an exacerbated increase in infiltrating immune cells and lung pathology as compared to wild-type controls. We further identified that, in response to dust, IL-22 is expressed in airway epithelium and in Ym1+ macrophages found within the parenchyma in response to dust. The increase in IL-22 expression was accompanied by increases in IL-22 Receptor IL-22R1 within the lung epithelium. In addition, we found that alveolar macrophages in vivo as well as THP-1 cells in vitro express IL-22, and this expression is modulated by dust exposure. Furthermore, subcellular localization of IL-22 appears to be in the Golgi of resting THP1 human monocytes, and treatment with dust extracts is associated with IL-22 release into the cytosolic compartment from the Golgi reservoirs during dust extract exposure. Taken together, we have identified a significant role for macrophage-mediated IL-22 signaling that is activated in dust-induced lung inflammation in mice.