Distinct Expression of Coinhibitory Molecules on Alveolar T Cells in Patients With Rheumatoid Arthritis–Associated and Idiopathic Inflammatory Myopathy–Associated Interstitial Lung Disease

Maho Nakazawa, Katsuya Suzuki, Masaru Takeshita, Jun Inamo, Hirofumi Kamata, Makoto Ishii, Yoshitaka Oyamada, Hisaji Oshima, Tsutomu Takeuchi

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Objective: To identify immunologic factors in the lungs of patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD) and patients with idiopathic inflammatory myopathy–associated ILD (IIM-ILD) and to examine their pathologic mechanisms. Methods: Eleven patients with RA-ILD, 16 with IIM-ILD, 6 with drug-induced ILD (DI-ILD), and 8 healthy controls were enrolled. Peripheral blood (PB) and bronchoalveolar lavage (BAL) fluid were immunophenotyped by flow cytometry. Alveolar macrophages (AMs) were analyzed by coculture assay with PB naive CD4+ T cells from healthy individuals and RNA sequencing. Results: Several coinhibitory molecules were coexpressed on BAL fluid T cells (CTLA-4, programmed death 1 [PD-1], T cell immunoglobulin and mucin domain–containing protein 3 [TIM-3], and lymphocyte activation gene 3 protein, from most to least), whereas only PD-1 was expressed on PB T cells. CTLA-4+PD-1+CD4+ T cells were characteristic of RA-ILD, whereas CTLA-4+PD-1+TIM-3+CD8+ T cells were characteristic of IIM-ILD. BAL fluid PD-1+CD4+ T cells rarely expressed CXCR5, but their levels correlated with levels of plasmablasts and plasma cells (ρ = 0.57, P = 0.006), indicating that most of them would be considered peripheral helper T cells. In coculture experiments, AMs from patients with RA-ILD and IIM-ILD induced more PD-1 and TIM-3 on T cells (P < 0.05), suggesting that coinhibitory molecule expression on BAL fluid T cells was partly due to AMs. RNA sequencing showed significant down-regulation of PD ligand 1/2 genes in AMs from patients with RA-ILD compared to those with DI-ILD. Conclusion: We have identified differences in coinhibitory molecule expression between patients with RA-ILD and those with IIM-ILD. PD-1 on T cells in RA-ILD and TIM-3 on CD8+ T cells in IIM-ILD might be key factors in the disease process. Evaluation of coinhibitory molecules on BAL fluid T cells could be clinically useful.

Original languageEnglish
Pages (from-to)576-586
Number of pages11
JournalArthritis and Rheumatology
Volume73
Issue number4
DOIs
Publication statusPublished - 2021 Apr

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Fingerprint Dive into the research topics of 'Distinct Expression of Coinhibitory Molecules on Alveolar T Cells in Patients With Rheumatoid Arthritis–Associated and Idiopathic Inflammatory Myopathy–Associated Interstitial Lung Disease'. Together they form a unique fingerprint.

Cite this