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

doi:10.1016/j.celrep.2023.112990

Enhancing autophagy in CD11c⁺ antigen-presenting cells as a therapeutic strategy for acute respiratory distress syndrome

Cell Rep. 2023 Aug 29;42(8):112990. doi: 10.1016/j.celrep.2023.112990. Epub 2023 Aug 16.

Affiliations

¹ Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
² USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, CA 90089, USA.
³ Janssen Research and Development, San Diego, CA 92121, USA.
⁴ University of Pittsburgh School of Medicine and UPMC, Pittsburgh, PA 15261, USA; Pittsburgh VA Medical Center, Pittsburgh, PA 15240, USA.
⁵ Division of Neonatology, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
⁶ Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: [email protected].

Abstract

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.

Keywords: CD11c; CP: Immunology; acute respiratory distress syndrome (ARDS); antigen-presenting cells; autophagy; lung inflammation; lung injury; poly(I:C).

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Acute Lung Injury*
Animals
Antigen-Presenting Cells
Autophagy
Macrophages
Mice
Poly I-C / pharmacology
Respiratory Distress Syndrome*

Substances

Poly I-C