Enhancing autophagy in CD11c+ antigen-presenting cells as a therapeutic strategy for acute respiratory distress syndrome
Christine Quach,
Doumet Georges Helou,
Meng Li,
Benjamin Pierre Hurrell,
Emily Howard,
Pedram Shafiei-Jahani,
Pejman Soroosh,
Jing-hsiung James Ou,
Babak Razani,
Virender Rehan,
Omid Akbari
Affiliations
Christine Quach
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Doumet Georges Helou
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Meng Li
USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, CA 90089, USA
Benjamin Pierre Hurrell
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Emily Howard
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Pedram Shafiei-Jahani
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Pejman Soroosh
Janssen Research and Development, San Diego, CA 92121, USA
Jing-hsiung James Ou
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Babak Razani
University of Pittsburgh School of Medicine and UPMC, Pittsburgh, PA 15261, USA; Pittsburgh VA Medical Center, Pittsburgh, PA 15240, USA
Virender Rehan
Division of Neonatology, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA
Omid Akbari
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Corresponding author
Summary: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe clinical disorders that mainly develop from viral respiratory infections, sepsis, and chest injury. Antigen-presenting cells play a pivotal role in propagating uncontrolled inflammation and injury through the excess secretion of pro-inflammatory cytokines and recruitment of immune cells. Autophagy, a homeostatic process that involves the degradation of cellular components, is involved in many processes including lung inflammation. Here, we use a polyinosinic-polycytidylic acid (poly(I:C))-induced lung injury mouse model to mimic viral-induced ALI/ARDS and show that disruption of autophagy in macrophages exacerbates lung inflammation and injury, whereas autophagy induction attenuates this process. Therefore, induction of autophagy in macrophages can be a promising therapeutic strategy in ALI/ARDS.
