Year: 2023
Type: conference-abstract
Abstract: Acute Respiratory Distress Syndrome (ARDS) is a fatal condition in which damage to the lungs results in fluid buildup and eventually hypoxia. Elucidating the immunological mechanism of this disorder is vital for reducing fatality. Staphylococcus enterotoxin B (SEB)-induced ARDS mimics the cytokine storm presented in patients with severe COVID-19. In previous studies, we found that SEB induced the infiltration of multiple CCR2+ macrophage subgroups and neutrophils in the lungs. Here, we investigated the role of CCR2 in the regulation of lung inflammation in SEB-induced ARDS, by utilizing CCR2-deficient mice. Mice were administered 50μg i.n. of SEB and evaluated for clinical distress and lung function over 72 hours. We performed flow cytometry and scRNA-seq on cells isolated from the whole lung of CCR2+/+ and CCR2−/−mice. We found a decrease in Ly6c+monocytes, macrophages, and CCR2+ macrophages in CCR2−/−mice, using flow and scRNA-seq analysis. Interestingly, alveolar macrophages were increased in the CCR2−/−mice. The CCR2−/−mice illustrated significant differences in their lung immune cell landscape. Mice exhibited increases in multiple T cell populations not observed in the wild-type mice. CCR2−/−mice expressed novel naïve T cells and a population of T cells which expressed genes associated with chromosome condensation (Hist1h2ap, Hist1h2ae, and Hist1h4d). Overall, top genes expressed in CCR2−/−mice such as Tcf7, Trbc2, and Stmn1, have been associated with T cell differentiation and tolerance induction. These results suggest that CCR2 deficiency prevents the migration of inflammatory monocytes to the lung but in return increase the presence of multiple unique T cell populations which alters the innate response in ARDS. NIH P01AT003961, P20GM103641, R01AI129788, R01ES030144, R01AI123947, and K99GM147910
Source: The Journal of Immunology
Institution: University of South Carolina
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4385686223