Transcriptional analysis of Foxp3+ Tregs and functions of two identified molecules during resolution of ALI
Year: 2019
Type: article
Abstract: Recovery from acute lung injury (ALI) is an active process. Foxp3+ Tregs contribute to recovery from ALI through modulating immune responses and enhancing alveolar epithelial proliferation and tissue repair. The current study investigates Treg transcriptional profiles during resolution of ALI in mice. Tregs from either lung or splenic tissue were isolated from uninjured mice or mice recovering from ALI and then examined for differential gene expression between these conditions. In mice with ALI, Tregs isolated from the lungs had hundreds of differentially expressed transcripts compared with those from the spleen, indicating that organ specificity and microenvironment are critical in Treg function. These regulated transcripts suggest which intracellular signaling pathways modulate Treg behavior. Interestingly, several transcripts having no prior recognized function in Tregs were differentially expressed by lung Tregs during resolution. Further investigation into 2 identified transcripts, Mmp12 and Sik1, revealed that Treg-specific expression of each plays a role in Treg-promoted ALI resolution. This study provides potentially novel information describing the signals that may expand resident Tregs, recruit or retain them to the lung during ALI, and modulate their function. The results provide insight into both tissue- and immune microenvironment-specific transcriptional differences through which Tregs direct their effects.
Source: JCI Insight
Institutions: Lung Institute, University of North Carolina at Chapel Hill
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,100
Awards: Defining the Role of Regulatory T Cell-Derived MMP12 in Acute Lung Injury Resolution, Production of Targeted Null Mutations for 10,000 Genes in C57BL/6 ES Cells, Trafficking and function of macrophage subpopulations within the lung microenvironment during pneumonia, Rho-mediated Signaling in Lung Endothelial Cells Induced by Neutrophil Adhesion, Regulatory T Cells Promote Alveolar Epithelial Repair, Application of Omics in Lung Disease, UCD KOMP Project Repository, High-throughput targeted mutagenesis of mouse stem cell lines, KOMP2-Phase3 Production and Phenotyping by the DTCC Consortium., A Carolina Center to Characterize and Maintain Mutant Mice, Cancer Center Support Grant
OpenAlex ID: W2912580500