THU0049 DISTINCT EXPRESSION OF COINHIBITORY MOLECULES ON ALVEOLAR T CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS- AND IDIOPATHIC INFLAMMATORY MYOPATHIES-ASSOCIATED INTERSTITIAL LUNG DISEASE. (13th June 2020)

• Record Type: Journal Article
• Authors: Nakazawa, M.; Suzuki, K.; Takeshita, M.; Inamo, J.; Kamata, H.; Ishii, M.; Oyamada, Y.; Oshima, H.; Takeuchi, T.
• Is Part Of: Annals of the rheumatic diseases. Volume 79(2020)Supplement 1
• Page Start: 236
• Page End: 237
• Publication Date: 2020-06-13
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2020-eular.4542
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: 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.