Single-cell transcriptomics reveals peripheral immune responses in anti-synthetase syndrome-associated interstitial lung disease

ABSTRACT: Objective: Interstitial lung diseases (ILDs) secondary to anti-synthetase syndrome (ASS) greatly influence the prognoses of patients with ASS. Here we aimed to investigate the peripheral immune responses to understand the pathogenesis of this condition. Methods: We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from 5 patients with ASS-ILD and 3 healthy donors (HDs). Flow cytometry of PBMCs was performed to replenish the results of scRNA-seq. Results: We used scRNA-seq to depict a high-resolution visualization of cellular landscape in PBMCs from patients with ASS-ILD. Patients showed upregulated interferon responses among all cell types. And the ratio of effector memory CD8 T cells to naïve CD8 T cells was significantly higher than that in HDs. Additionally, Th1, Th2, and Th17 cell differentiation signaling pathways were enriched in T cells, and antigen processing and presentation was enhanced in NK cells. Flow cytometry analyses showed increased proportions of Th17 cells and Th2 cells, and decreased proportion of Th1 cells in patients with ASS-ILD when compared with HDs. Conclusions: Our study reveals that ASS-ILD is characterized by upregulated interferon responses, altered CD8 T cell homeostasis, involvement of differentiation signaling pathways of CD4 T cells, and enhanced antigen processing and presentation ability in NK cells by scRNA-seq data. And the proportions of Th17 cells and Th2 cells are higher in patients with ASS-ILD than those in HDs using flow cytometry, while the proportion of Th1 cells is lower. These findings may provide foundations of novel therapeutic targets for patients with this condition.

ORGANISM(S): Homo sapiens

PROVIDER: GSE190510 | GEO | 2021/12/10

REPOSITORIES: GEO