IL-22 regulates inflammatory responses to agricultural dust-induced airway inflammation

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number116044
JournalToxicology and Applied Pharmacology
Volume446
DOIs
StatePublished - Jul 1 2022

Keywords

  • Agricultural dust
  • IL-22
  • IL-22R1
  • Macrophage
  • Resolution of inflammation

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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