Bibliographic Details
| Title: |
Spatial Transcriptomics Resolve an Emphysema-Specific Lymphoid Follicle B Cell Signature in Chronic Obstructive Pulmonary Disease. |
| Authors: |
Rojas-Quintero, Joselyn, Ochsner, Scott A., New, Felicia, Divakar, Prajan, Chen Xi Yang, Wu, Tianshi David, Robinson, Jerid, Chandrashekar, Darshan Shimoga, Banovich, Nicholas E., Rosas, Ivan O., Sauler, Maor, Kheradmand, Farrah, Gaggar, Amit, Margaroli, Camilla, Estepar, Raul San Jose, McKenna, Neil J., Polverino, Francesca |
| Source: |
American Journal of Respiratory & Critical Care Medicine; 1/1/2024, Vol. 209 Issue 1, p48-58, 30p |
| Subject Terms: |
CHRONIC obstructive pulmonary disease, B cells, TRANSCRIPTOMES, GENE regulatory networks, GENE expression |
| Abstract: |
Rationale: Within chronic obstructive pulmonary disease (COPD), emphysema is characterized by a significant yet partially understood B cell immune component. Objectives: To characterize the transcriptomic signatures from lymphoid follicles (LFs) in ever-smokers without COPD and patients with COPD with varying degrees of emphysema. Methods: Lung sections from 40 patients with COPD and eversmokers were used for LF proteomic and transcriptomic spatial profiling. Formalin- and O.C.T.-fixed lung samples obtained from biopsies or lung explants were assessed for LF presence. Emphysema measurements were obtained from clinical chest computed tomographic scans. High-confidence transcriptional target intersection analyses were conducted to resolve emphysema-induced transcriptional networks. Measurements and Main Results: Overall, 115 LFs from eversmokers andGlobal Initiative for ChronicObstructive LungDisease (GOLD) 1-2 andGOLD3-4 patients were analyzed. No LFs were found in never-smokers. Differential gene expression analysis revealed significantly increased expression of LF assembly and B cellmarker genes in subjects with severe emphysema. High-confidence transcriptional analysis revealed activation of an abnormal B cell activity signature in LFs (q-value= 2.56E-111). LFs frompatients withGOLD 1-2 COPDwith emphysema showed significantly increased expression of genes associated with antigen presentation, inflammation, and B cell activation and proliferation. LFs frompatients with GOLD1-2COPD without emphysema showed an antiinflammatory profile. The extent of centrilobular emphysema was significantly associated with genes involved in B cellmaturation and antibody production. Protein-RNA network analysis showed that LFs in emphysema have a unique signature skewed toward chronic B cell activation. Conclusions: An off-targeted B cell activation within LFs is associated with autoimmune-mediated emphysema pathogenesis. [ABSTRACT FROM AUTHOR] |
|
Copyright of American Journal of Respiratory & Critical Care Medicine is the property of American Thoracic Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |
