한빛사논문
- 조회527
Kijong Yi MD, PhD1*, Sungsin Jo PhD2*, Woogil Song BS3*, Hae-I n Lee MS4, Hui-Ju Kim MS4, Ji-Hyoun Kang MD PhD4, Seon Uk Kim MS5, Seung Hoon Lee PhD2, Jinsung Park PhD2, Tae-Hwan Kim MD PhD2,6, Jeong Seok Lee MD PhD1,3†, Eun Young Lee MD PhD5†, Tae-Jong Kim MD PhD4†
1Genome Insight, Inc., San Diego, CA 92121, USA
2Hanyang University Institute for Rheumatology Research (HYIRR), Seoul 04763, Republic of Korea
3Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
4Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju 58128, Republic of Korea.
5Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
6Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 04763, Republic of Korea
*These authors contributed equally to this work.
†Corresponding authors: Jeong Seok Lee MD PhD; Eun Young Lee MD PhD;Ta e-Jong Kim MD PhD
Abstract
Objectives: To demonstrate the immune landscape of blood and synovial cells in AS through both single cell transcriptome and surface protein expression analysis to unveil the molecular characteristics of pathogenic Th17 cells (pTh17) METHODS: 40 active AS, 20 stable AS, 40 active RA patients, and 20 healthy control were included in the study. Surface phenotype and intracellular staining after T cell receptor stimulation of peripheral blood mononuclear cells and synovial fluid mononuclear cells were assessed using flow cytometr. Single cell transcriptome of six patients with active AS were studied along with and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq). We also assessed the outcome of targeting OX40 and GITR on the cell surface of Th17 cells in the curdlan-injected SKG mouse model using anti-GITRL and/or anti-OX40L.
Results: We identified pTh17 cells as polyfunctional IL-17A and IFN-γ-producing memory CD4+ T cells, with clinically supporting evidence for their pathogenic roles at the inflammatory site of AS. Transcriptome and flow cytometric analysis found that the co-expression of TNFRSF4 (OX40) and TNFRSF18 (GITR, glucocorticoid-induced TNF receptor) is increased in pTh17 cells. In vivo suppression of ligand-receptor interactions via OX40 and GITR effectively suppressed clinical arthritis and decreased pTh17 cells in the curdlan-injected SKG mouse model.
Conclusions: Our results have implications for understanding pTh17 cells in AS and suggest potential therapeutic targets.
논문정보
- Research article
- 2023년 02월 (BRIC 등록일 2023-02-27)
- 국내(교신)+국외 연구진
- 의약학 > 면역의학
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