In:
Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 236.3-237
Abstract:
Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA) and also the most common non-musculoskeletal manifestation of idiopathic inflammatory myopathies (IIM), including polymyositis, dermatomyositis and clinically amyopathic dermatomyositis. Previous studies have suggested that alveolar macrophages (AMs) and T cells are associated with the pathogenesis of ILD. Recently, it is reported that coinhibitory molecules are expressed at the site of inflammation such as RA synovium; however, detailed lung immunophenotyping has not been reported. Objectives: To identify immunologic factors in the lungs of patients with RA-associated ILD (RA-ILD) and IIM-associated ILD (IIM-ILD) and to examine their pathological mechanisms. Methods: A total of 11 patients with RA-ILD, 16 with IIM-ILD, and 6 with drug-induced ILD (DI-ILD) and 8 healthy controls were enrolled. Peripheral blood and bronchoalveolar lavage fluid (BALF) were immunophenotyped by flow cytometry. AMs were analyzed by RNA-sequence and coculture assay with peripheral naïve CD4+ T cells of healthy individuals. Results: Several coinhibitory molecules were coexpressed on BALF T cells in the order of CTLA-4, PD-1, Tim-3, and LAG-3 from most to least, whereas only PD-1 was expressed on peripheral T cells among them. In RA-ILD, PD-1+ and Tim-3+ CD4+ T cells in the BALF were increased. PD-1+CD4+ T cells populations correlated differentiated B cells and Tim-3+CD4+ T cells populations correlated with ILD severity and RF titer. In contrast, in IIM-ILD, activated CD8+ T cells were increased and they coexpressed CTLA-4, PD-1 and Tim-3. BALF PD-1+CD4+ T cells rarely expressed CXCR5, and they positively correlated with plasmablasts and plasma cells, indicating most of them are considered Tph cells. In the coculture experiments, AMs of RA-ILD and IIM-ILD induced more PD-1 and Tim-3 on CD4+ T cells, suggesting that coinhibitory molecule expression on BALF T cells was partly due to AMs. In RNA-sequence, PD-ligand (PD-L) 1 and PD-L2 genes were significantly downregulated in AMs from RA-lLD compared with DI-ILD. Conclusion: We identified T cell subsets that play a central role in the pathogenesis of RA-ILD and 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. The evaluation of coinhibitory molecules on BALF T cells could be clinically useful. Disclosure of Interests: Maho Nakazawa: None declared, Katsuya Suzuki: None declared, Masaru Takeshita: None declared, Jun Inamo: None declared, Hirofumi Kamata: None declared, Makoto Ishii: None declared, Yoshitaka Oyamada: None declared, Hisaji Oshima: None declared, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi & Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd.
Type of Medium:
Online Resource
ISSN:
0003-4967
,
1468-2060
DOI:
10.1136/annrheumdis-2020-eular.4542
Language:
English
Publisher:
BMJ
Publication Date:
2020
detail.hit.zdb_id:
1481557-6
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