Single-cell profiling reveals immune aberrations in progressive idiopathic pulmonary fibrosis

• DOI: 10.1101/2023.04.29.23289296
• Publication Date: 2023-04-29T22:40:12Z
• Authors: Avraham Unterman; Amy Y. Zhao; Nir Neumark; Jonas C. Schupp; Farida Ahangari; Carlos Cosme; Prapti Sharma; Jasper Flint; Yan Stein; Changwan Ryu; Genta Ishikawa; Tomokazu S. Sumida; Jose L. Gomez; Jose Herazo-Maya; Charles S. Dela Cruz; Erica L. Herzog; Naftali Kaminski
• Keywords: Article; 3. Good health

Abstract Rationale Changes in peripheral blood cell populations have been observed but not detailed at single-cell resolution idiopathic pulmonary fibrosis (IPF). Objectives To provide an atlas of the changes immune system stable and progressive IPF. Methods Peripheral mononuclear cells (PBMCs) from IPF patients controls were profiled using 10x Chromium 5’ RNA sequencing (scRNA-seq). Flow cytometry was used for validation. Protein concentrations Regulatory T-cells (Tregs) Monocytes chemoattractants measured plasma lung homogenates controls. Measurements Main Results Thirty-eight PBMC samples 25 with 13 matched yielded 149,564 that segregated into 23 subpopulations, corresponding to all expected populations. Classical monocytes increased compared (32.1%, 25.2%, 17.9%, respectively, p<0.05). Total lymphocytes decreased vs controls, (52.6% 62.6%, p=0.035). Tregs (1.8% 1.1%, p=0.007), associated survival (P=0.009 Kaplan-Meier analysis). analysis confirmed this finding independent cohort patients. also two cohorts scRNA-seq. CCL22 CCL18, ligands CCR4 CCR8 Treg chemotaxis receptors, Conclusions The IPF, reveals outcome-predictive increase classical Tregs, as well evidence a lung-blood recruitment axis involving CCL7 (for monocytes) CCL18/CCL22 Tregs).