2. Academic Validation
  3. Airway epithelial immunoproteasome subunit LMP7 protects against rhinovirus infection

Airway epithelial immunoproteasome subunit LMP7 protects against rhinovirus infection

  • Sci Rep. 2022 Aug 25;12(1):14507. doi: 10.1038/s41598-022-18807-3.
Kris Genelyn Dimasuay 1,  Niccolette Schaunaman 2,  Bruce Berg 2,  Diana Cervantes 2,  Elke Kruger 3,  Frank L Heppner 4,  Deborah A Ferrington 5,  Hong Wei Chu 6
Affiliations

Affiliations

  • 1 Department of Medicine, National Jewish Health, Denver, CO, USA. dimasuayg@njhealth.org.
  • 2 Department of Medicine, National Jewish Health, Denver, CO, USA.
  • 3 Institute for Medicine Biochemistry and Molecular Biology, Universitätsmedizin Greifswald, Greifswald, Germany.
  • 4 Department of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • 5 Doheny Eye Institute, University of California Los Angeles, Pasadena, CA, USA.
  • 6 Department of Medicine, National Jewish Health, Denver, CO, USA. chuh@njhealth.org.
PMID: 36008456 DOI: 10.1038/s41598-022-18807-3
Abstract

Immunoproteasomes (IP) serve as an important modulator of immune responses to pathogens and other pathological factors. LMP7/β5i, one of the IP subunits, plays a critical role in autoimmune diseases by downregulating inflammation. Rhinovirus (RV) Infection is a major risk factor in the exacerbations of respiratory inflammatory diseases, but whether LMP7 regulates RV-mediated inflammation in the lung particularly in the airway epithelium, the first line of defense against RV Infection, remains unclear. In this study, we determined whether airway epithelial LMP7 promotes the resolution of RV-mediated lung inflammation. Inducible airway epithelial-specific LMP7-deficient (conditional knockout, CKO) mice were generated to reveal the in vivo anti-inflammatory and Antiviral functions of LMP7. By using LMP7-deficient primary human airway epithelial cells generated by CRISPR-Cas9, we confirmed that airway epithelial LMP7 decreased pro-inflammatory cytokines and viral load during RV Infection. Additionally, airway epithelial LMP7 enhanced the expression of a negative immune regulator A20/TNFAIP3 during viral Infection that may contribute to the anti-inflammatory function of LMP7. We also discovered that induction of LMP7 by a low dose of polyinosinic:polycytidylic acid (PI:C) reduced RV-mediated inflammation in our CKO mice infected with RV. Our findings suggest that airway epithelial LMP7 has anti-inflammatory and Antiviral functions that is critical to the resolution of RV-mediated lung inflammation. Induction of airway epithelial LMP7 may open a novel avenue for therapeutic intervention against RV Infection.

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