Spatial Transcriptomics Resolve an Emphysema-Specific Lymphoid Follicle B Cell Signature in Chronic Obstructive Pulmonary Disease

作者：Joselyn Rojas, Scott A. Ochsner, Felicia New, Prajan Divakar, Chen Xi Yang, Tianshi David Wu, Jerid W. Robinson, Darshan S. Chandrashekar, Nicholas E. Banovich, Iván O. Rosas, Maor Sauler, Farrah Kheradmand, Amit Gaggar, Camilla Margaroli, Raúl San Jośe Estépar, Neil J. McKenna, Francesca Polverino · 发表于：American Journal of Respiratory and Critical Care Medicine · 年份：2023 · DOI：10.1164/rccm.202303-0507le · 被引用次数：41 · 研究领域：Chronic Obstructive Pulmonary Disease (COPD) Research、IL-33, ST2, and ILC Pathways、Neonatal Respiratory Health Research

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 ever-smokers 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 ever-smokers and Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1–2 and GOLD 3–4 patients were analyzed. No LFs were found in never-smokers. Differential gene expression analysis revealed significantly increased expression of LF assembly and B cell marker 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 from patients with GOLD 1–2 COPD with emphysema showed significantly increased expression of genes associated with antigen presentation, inflammation, and B cell activation and proliferation. LFs from p...