Characterization of Chemotaxis-Associated Gene Dysregulation in Myeloid Cell Populations in the Lungs during Lipopolysaccharide-Mediated Acute Lung Injury
Year: 2023
Type: article
Abstract: During endotoxin-induced acute lung injury (ALI), immune cell recruitment resulting from chemotaxis is mediated by CXC and CC chemokines and their receptors. In this study, we investigated the role of chemokines and their receptors in the regulation of myeloid cell populations in the circulation and the lungs of C57BL/6J mice exhibiting LPS-mediated ALI using single-cell RNA sequencing. During ALI, there was an increase in the myeloid cells, M1 macrophages, monocytes, neutrophils, and other granulocytes, whereas there was a decrease in the residential alveolar macrophages and M2 macrophages. Interestingly, LPS triggered the upregulation of CCL3, CCL4, CXCL2/3, and CXCL10 genes associated with cellular migration of various subsets of macrophages, neutrophils, and granulocytes. Furthermore, there was an increase in the frequency of myeloid cells expressing CCR1, CCR3, CCR5, and CXCR2 receptors during ALI. MicroRNA sequencing studies of vehicle versus LPS groups identified several dysregulated microRNAs targeting the upregulated chemokine genes. This study suggests that chemokine ligand-receptors interactions are responsible for myeloid cell heterogenicity and cellular recruitment to the lungs during ALI. The single-cell transcriptomics allowed for an in-depth assessment and characterization of myeloid cells involved in immune cell trafficking during ALI.
Source: The Journal of Immunology
Institution: University of South Carolina
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Institutes of Health, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Environmental Health Sciences, National Center for Complementary and Integrative Health, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases
Awards: Role of macrophages in CBD mediated attenuation of SEB-induced ARDS, CAM Center for Epigenetic Regulation of Inflammation, Immunopathological basis of PTSD, Epigenetic mechanisms in Transgenerational Effects of an Environmental Pollutant, G477997293, Dietary Supplements and Inflammation Phase-2, Effect of TCDD-induced apoptosis on T cells, Cannabinoid-induced apoptosis in T cell regulation, Epigenetic Mechanisms of T Cell Dysregulation in PTSD, AhR ligands in epigenetic dysregulation of T cells, Estrogen-T cell Interactions, G8455666878, G883620226, G8843880088, Role of the environmental sensor, AhR on colitis, Role of Macrophages in CBD mediated attenuation of SEB-induced ARDS
OpenAlex ID: W4376121683