FRI0080 CD11B+GR1DIM tolerogenic dendritic cell-like cells are expanded in interstitial lung disease in SKG mice. (15th June 2017)

• Record Type: Journal Article
• Authors: Sendo, S; Saegusa, J; Ichise, Y; Yamada, H; Naka, I; Okano, T; Takahashi, S; Ueda, Y; Akashi, K; Onishi, A; Morinobu, A
• Is Part Of: Annals of the rheumatic diseases. Volume 76(2017)Supplement 2
• Page Start: 507
• Page End: 508
• Publication Date: 2017-06-15
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2017-eular.1429
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: SKG mice develop interstitial lung disease (ILD) resembling human rheumatoid arthritis (RA)–associated ILD. We identified a unique cell population of CD11b + Gr1 dim cells in the severely inflamed lungs in SKG mice. Objectives: The aims of this study are to clarify the mechanism behind the lung pathology, and to elucidate the phenotype and function of CD11b + Gr1 dim cells in ILD-induced SKG mice. Methods: We assessed the severity of zymosan A-induced ILD in SKG mice histologically, and examined lung-infiltrating cells by Giemsa stain and flow cytometry. Total lung cells and isolated monocytic myeloid-derived suppressor cells (M-MDSCs) were cultured in vitro with GM-CSF (and IL-4). The proliferation of CSFE-labeled naïve T cells co-cultured with isolated CD11b + Gr1 dim cells and MDSCs was evaluated by flow cytometry. Results: MDSCs, Th17 cells, and group 1 and 3 innate lymphoid cells (ILC1s and ILC3s) were increased in the lungs; the proportion of these cells varied with ILD severity. In this process, we found that a unique cell population, CD11b + Gr1 dim cells, were expanded in the severely inflamed lungs (Figure). About half of the CD11b + Gr1 dim cells expressed CD11c and Giemsa stain revealed that they were morphologically dendritic cell (DC)-like. The CD11b + Gr1 dim cells were induced from M-MDSCs with GM-CSF in vitro and were considered tolerogenic because they expressed high levels of PD-L1 and suppressed T-cell proliferation. The CD11b + Gr1 dim cells have never described previously and termed CD11b + Gr1 dim tolerogenic DC-like cells (CD11b + Gr1 dim tolDC-LCs). Th17 cells, ILC1s and ILC3s in the inflamed lung produced GM-CSF, which in turn could induce CD11b + Gr1 dim tolDC-LCs to reduce inflammation. Conclusions: We identified a unique cell population, termed CD11b + Gr1 dim tolDC-LCs, in ILD-induced lungs in SKG mice. References: Nishimura K, Saegusa J, Matsuki F, Akashi K, Kageyama G, Morinobu A. Tofacitinib facilitates the expansion of myeloid-derived suppressor cells and ameliorates arthritis in SKG mice. Arthritis Rheumatol 2015;67:893–902. Shiomi A, Usui T, Ishikawa Y, Shimuzu M, Murakami K, Mimori T. GM-CSF but not IL-17 is critical for the development of severe interstitial lung disease in SKG mice. J. Immunol 2014;193:849–59. Takenaka MC, Quintana FJ. Tolerogenic dendritic cells. Semin. Immunopahol 2016. doi:10.1007/s00281–016–0587–8. Acknowledgements: The authors thank Shino Tanaka (Department Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine) for providing technical assistance. Disclosure of Interest: None declared