Journal article
Epithelial LIF signaling limits apoptosis and lung injury during bacterial pneumonia
American journal of physiology. Lung cellular and molecular physiology, Vol.322(4), pp.L550-L563
04/01/2022
DOI: 10.1152/ajplung.00325.2021
PMCID: PMC8957336
PMID: 35137631
Abstract
During bacterial pneumonia, alveolar epithelial cells are critical for maintaining gas exchange and providing antimicrobial as well as pro-immune properties. We previously demonstrated that leukemia inhibitory factor (LIF), an IL-6 family cytokine, is produced by type II alveolar epithelial cells (ATII) and is critical for tissue protection during bacterial pneumonia. However, the target cells and mechanisms of LIF-mediated protection remain unknown. Here, we demonstrate that antibody-induced LIF blockade remodels the lung epithelial transcriptome in association with increased apoptosis. Based on these data, we performed pneumonia studies using a novel mouse model in which LIFR (the unique receptor for LIF) is absent in lung epithelium. Although LIFR is expressed on the surface of epithelial cells, its absence only minimally contributed to tissue protection during pneumonia. Single-cell RNA-sequencing (scRNAseq) was conducted to identify adult murine lung cell types most prominently expressing Lifr, revealing endothelial cells, mesenchymal cells, and ATIIs as major sources of Lifr. Sequencing data indicated that ATII cells were significantly impacted by pneumonia, with additional differences observed in response to LIF neutralization, including but not limited to gene programs related to cell death, injury, and inflammation. Overall, our data suggest that LIF signaling on epithelial cells alters responses in this cell type during pneumonia. However, our results also suggest separate and perhaps more prominent roles of LIFR in other cell types, such as endothelial cells or mesenchymal cells, which provide grounds for future investigation.
Details
- Title: Subtitle
- Epithelial LIF signaling limits apoptosis and lung injury during bacterial pneumonia
- Creators
- Eri Allen - Boston UniversityLillia A. Baird - Boston University School of MedicineChristine V. Odom - Boston UniversityFiliz T. Korkmaz - Boston UniversityAnukul T. Shenoy - Boston UniversityAdeline M. Matschulat - Boston UniversityMatthew R. Jones - Boston UniversityDarrell N. Kotton - Boston UniversityJoseph P. Mizgerd - Boston UniversityXaralabos Varelas - Boston UniversityKatrina E. Traber - Boston UniversityLee J. Quinton - Boston University
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Lung cellular and molecular physiology, Vol.322(4), pp.L550-L563
- Publisher
- AMER PHYSIOLOGICAL SOC; Rockville
- DOI
- 10.1152/ajplung.00325.2021
- PMID
- 35137631
- PMCID
- PMC8957336
- ISSN
- 1040-0605
- eISSN
- 1522-1504
- Grant note
- National Institutes of Health (NIH): R01-HL111449, R01-GM120060, R01-HL124392, R35HL135756, R01-AI115053, R33-HL137081, T32-HL007035 National Heart Lung and Blood Institute: R35HL135756, R33HL137081
The study was supported by National Institutes of Health (NIH) Grants R01-HL111449, R01-GM120060, R01-HL124392, R35HL135756, R01-AI115053, R33-HL137081, and T32-HL007035.
- Language
- English
- Date published
- 04/01/2022
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984696657002771
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