The involvement of M2 CD163 positive macrophages in the development of arthritis

• Project/Area Number: 16K09912
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kurume University
• Principal Investigator: kaieda Shinjiro 久留米大学, 医学部, 講師 (20330798)
• Co-Investigator(Kenkyū-buntansha): 星野 友昭 久留米大学, 医学部, 教授 (00261066)
• Research Collaborator: KOMOHARA yoshihiro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 関節炎 / CD163陽性マクロファージ / ケモカイン / 炎症性サイトカイン / M2マクロファージ / マウス関節炎モデル / LPS / マクロファージ / M1 M2 バランス / 骨破壊 / 炎症細胞浸潤 / 内科 / 免疫学

Outline of Final Research Achievements

CD 163 KO mice significantly exhibited the exacerbation of clinical scores during arthritis, when compared with control WT B6 mice. Histomorphometric quantification of the arthritic changes in the joint tissues confirmed the clinical assessment, with significant increases in inflammation and bone erosion scores in CD 163 KO mice. CD163 deficiency exacerbates disease severity in an autoantibody-induced arthritis via up-regulation of synovial tissue IL-1β and IL-6. Further, CD163 positive macrophage deficiency induced neutrophil recruitment via up-regulation of CXCL1 in inflamed synovium. CD163-positive macrophages may play as an inhibitor in the pathogenesis of joint inflammation.

Academic Significance and Societal Importance of the Research Achievements

われわれはマウス関節炎実験で、CD163マクロファージ欠損による炎症性サイトカイン発現上昇を介した関節炎症増悪を確認し、CD163陽性マクロファージは関節炎症抑制的に作用することを明らかにした。CD163 KOマウスを用いた関節炎実験の報告はなく、本研究は独創的であり、マクロファージのM2分化調整を介した新規治療法開発への進展が期待される。マクロファージは生体内のすべての組織に存在し、その局所における環境因子により分化・成熟し、様々な病態・疾患（動脈硬化肥満腫瘍感染症など）に関与する。関節炎のみならず、他の疾患への治療応用が期待される。

Research Products

• [Journal Article] Signal intensity of superb micro-vascular imaging associates with the activity of vascular inflammation in Takayasu arteritis. (2019)
  • Author(s): Ito S, Tahara N, Hirakata S, Kaieda S, Tahara A, Maeda-Ogata S, Bekki M, Sugiyama Y, Honda A, Igata S, Kuromatsu R, Nakashima O, Fukumoto Y.
  • Journal Title: J Nucl Cardiol Volume: in press Issue: 3 Pages: 1063-1065
  • DOI: 10.1007/s12350-019-01665-4
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Limbic Encephalitis in Association with Systemic Lupus Erythematosus (2018)
  • Author(s): Sugi S, Kaieda S, Irie KI, Ida H.
  • Journal Title: Internal Medicine Volume: 57 Issue: 20 Pages: 3059-3059
  • DOI: 10.2169/internalmedicine.1009-18
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2018-10-15
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Characteristics of Relapsing Polychondritis: A Report of 8 Cases in Japan (2018)
  • Author(s): Tajiri M, Tominaga M, Kinoshita T, Nakamura M, Kaieda S, Okamoto M, Ida H, Kawayama T, Hoshino T
  • Journal Title: The Kurume Medical Journal Volume: 65 Issue: 2 Pages: 47-53
  • DOI: 10.2739/kurumemedj.MS652006
  • NAID: 130007650020
  • ISSN: 0023-5679, 1881-2090
  • Year and Date: 2018-06-30
  • Peer Reviewed / Open Access
• [Journal Article] Attenuated Airway Eosinophilic Inflammations in IL-38 Knockout Mouse Model (2018)
  • Author(s): MATSUOKA MASANOBU、KAWAYAMA TOMOTAKA、TOMINAGA MASAKI、KAIEDA SHINJIRO、TOKUNAGA YOSHIHISA、KAKU YOICHIRO、IMAOKA HARUKI、KINOSHITA TAKASHI、OKAMOTO MASAKI、AKIBA JUN、HOSHINO TOMOAKI
  • Journal Title: The Kurume Medical Journal Volume: 65 Issue: 2 Pages: 37-46
  • DOI: 10.2739/kurumemedj.MS652009
  • NAID: 130007650022
  • ISSN: 0023-5679, 1881-2090
  • Year and Date: 2018-06-30
  • Peer Reviewed / Open Access
• [Journal Article] Successful Treatment of Rapidly Progressive Unclassifiable Idiopathic Interstitial Pneumonia with Anti-melanoma Differentiation-associated Gene-5 Antibody by Intensive Immunosuppressive Therapy (2018)
  • Author(s): Koga T, Kaieda S, Okamoto M, Masuda K, Fujimoto K, Sakamoto S, Nakamura M, Tominaga M, Kawayama T, Fujimoto K, Hoshino T, Ida H.
  • Journal Title: Internal Medicine Volume: 57 Issue: 7 Pages: 1039-1043
  • DOI: 10.2169/internalmedicine.9553-17
  • NAID: 130006602620
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access
• [Journal Article] Initial predictors of poor survival in myositis-associated interstitial lung disease: a multicenter cohort of 497 patients (2018)
  • Author(s): Shinji Sato, Kenichi Masui, Naoshi Nishina, Yasushi Kawaguchi, Atsushi Kawakami, Maasa Tamura, Kei Ikeda, Takahiro Nunokawa, Yoshinori Tanino, Katsuaki Asakawa, Yuko Kaneko, Takahisa Gono, Taro Ukichi, Shinjiro Kaieda, Taio Naniwa, Masataka Kuwana, et al
  • Journal Title: Rheumatology (Oxford) Volume: NA Issue: 7 Pages: 1212-1221
  • DOI: 10.1093/rheumatology/key060
  • Peer Reviewed
• [Journal Article] The co-existence of Lemierre's syndrome and Bezold's abscesses due to Streptococcus constellatus: A case report. (2018)
  • Author(s): Yaita K, Sugi S, Hayashi M, Koga T, Ebata T, Sakai Y, Kaieda S, Ida H, Watanabe H.
  • Journal Title: Medicine Volume: 97 Issue: 26 Pages: 11288-11288
  • DOI: 10.1097/md.0000000000011228
  • Peer Reviewed / Open Access
• [Journal Article] Low positive titer of anti-melanoma differentiation-associated gene 5 antibody is not associated with a poor long-term outcome of interstitial lung disease in patients with dermatomyositis. (2018)
  • Author(s): Sakamoto S, Okamoto M, Kaieda S, Fujimoto K, Nagata S, Tominaga M, Nakamura M, Zaizen Y, Nouno T, Koga T, Kawayama T, Kuwana M, Ida H, Hoshino T.
  • Journal Title: Respir Investig Volume: 56 Issue: 6 Pages: 464-472
  • DOI: 10.1016/j.resinv.2018.07.007
  • Peer Reviewed
• [Journal Article] Successful Treatment of Rapidly Progressive Unclassifiable Idiopathic Interstitial Pneumonia with Anti-melanoma Differentiation-associated Gene-5 Antibody by Intensive Immunosuppressive Therapy (2018)
  • Author(s): Koga T, Kaieda S, Okamoto M, Masuda K, Fujimoto K, Sakamoto S, Nakamura M, Tominaga M, Kawayama T, Fujimoto K, Hoshino T, Ida H.
  • Journal Title: Internal Medicine Volume: 57 Pages: 1039-1043
  • NAID: 130006602620
  • Peer Reviewed / Open Access
• [Journal Article] Overexpression of IL-38 protein in anticancer drug-induced lung injury and acute exacerbation of idiopathic pulmonary fibrosis. (2017)
  • Author(s): Tominaga M, Okamoto M, Kawayama T, Matsuoka M, Kaieda S, Sakazaki Y, Kinoshita T, Mori D, Inoue A, Hoshino T.
  • Journal Title: Respiratory Investigation Volume: 55 Pages: 293-299
  • Peer Reviewed
• [Presentation] マスト細胞のシェーグレン症候群への関与 (2018)
  • Author(s): 海江田信二郎
  • Organizer: 第62回日本リウマチ学会総会
• [Presentation] 当院における多発血管炎性肉芽腫症に対するリツキシマブ治療効果の検討 (2018)
  • Author(s): 林真樹子、藤本京子、海江田信二郎、吉田裕美、杉 鈴奈、古賀琢眞、日髙由紀子、星野友昭、井田弘明
  • Organizer: 第62回日本リウマチ学会総会
• [Presentation] 不明熱患者における自己炎症症候群11疾患遺伝子の網羅的解析 (2018)
  • Author(s): 日高由紀子、山崎聡士、藤本京子、古賀琢眞、吉田直実、中島宗敏、海江田信二郎、西小森隆太、井田弘明.
  • Organizer: 第62回日本リウマチ学会総会
• [Presentation] 当科で経験した家族性地中海熱22例の検討 (2018)
  • Author(s): 藤本京子、日高由紀子、林真樹子、杉 鈴奈、古賀琢眞、海江田信二郎、星野友昭、山崎聡士、井田弘明
  • Organizer: 第62回日本リウマチ学会総会
• [Presentation] 抗MDA5抗体陽性皮膚筋炎合併間質性肺障害に対するIVCY早期導入の意義 (2018)
  • Author(s): 古賀琢眞、林真樹子、吉田裕美、海江田信二郎、井田弘明
  • Organizer: 第62回日本リウマチ学会総会
• [Presentation] Involvement of mast cells in the development of tissue fibrosis of Sjogren's syndrome via inducing fibroblasts collagen synthesis (2018)
  • Author(s): Shinjiro Kaieda
  • Organizer: American college of Rheumatology annual meeting
  • Int'l Joint Research
• [Presentation] シェーグレン症候群におけるマスト細胞の関与 (2018)
  • Author(s): 海江田信二郎
  • Organizer: 第62回日本リウマチ学会総会
• [Presentation] Involvement of CD163-positive Macrophages in the pathogenesis of Arthritis via modulation of inflammatory cytokine expression in the synovium of a murine model (2017)
  • Author(s): Shinjiro Kaieda
  • Organizer: 2017 日本リウマチ学会総会（JCR）
  • Place of Presentation: 福岡
  • Year and Date: 2017-04-19
• [Presentation] CD163陽性M2マクロファージの関節炎における機能解析と治療への応用 (2017)
  • Author(s): 海江田信二郎 星野友昭
  • Organizer: 2017 日本免疫学会総会
• [Presentation] Involvement of CD163-Positive Macrophages in the Pathogenesis of Arthritis Via Modulation of Inflammatory Cytokine and Chemokine Expression in the Synovium of a Murine Model (2016)
  • Author(s): Shinjiro Kaieda
  • Organizer: 2016 アメリカリウマチ学会総会（ACR)
  • Place of Presentation: Washington DC
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Book] 肥満細胞と炎症 (2017)
  • Author(s): 海江田信二郎
  • Total Pages: 4
  • Publisher: 科学評論社