2. Academic Validation
  3. IL-22 regulates inflammatory responses to agricultural dust-induced airway inflammation

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.
Arzu Ulu 1,  Stefanie Sveiven 1,  Amanpreet Bilg 1,  Jalene V Velazquez 1,  Marissa Diaz 2,  Maheswari Mukherjee 3,  Ana G Yuil-Valdes 4,  Santosh Kota 5,  Abigail Burr 1,  Aileen Najera 1,  Tara M Nordgren 6
Affiliations

Affiliations

  • 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].
PMID: 35525330 DOI: 10.1016/j.taap.2022.116044
Abstract

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.

Keywords

Agricultural dust; IL-22; IL-22R1; Macrophage; Resolution of inflammation.

Figures