Experimental study on prevention and therapy of autoimmune diseases using lowly pathogenic parasitic helminths

• Project/Area Number: 25460523
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: Osada Yoshio 産業医科大学, 医学部, 准教授 (80282515)
• Co-Investigator(Renkei-kenkyūsha): KURODA ETSUSHI 大阪大学, 免疫学フロンティア研究センター, 准教授 (10299604) ; YAMADA SOHSUKE 産業医科大学, 医学部, 講師 (90525453)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 免疫修飾 / 感染症 / 炎症 / 寄生虫 / 自己免疫疾患 / 糖尿病 / 関節炎 / サイトカイン / 蠕虫 / 住血吸虫

Outline of Final Research Achievements

By comparison of multiple helminth species, we tried to find essential factors for anti-inflammatory properties of parasitic helminths. An intestinal nematode Heligmosomoides polygyrus (Hp) and Schistosoma mansoni (Sm) showed anti-diabetic effects on experimental type 1 diabetes in mice.These effects were observed not only in wild-type genetic background but also in dual genetic absence of STAT6 and IL-10. In such a genetic condition, non-typical M2-like macrophages were induced in the pancreatic lymph nodes and spleens and the cells might be involved in anti-diabetic effects of helminths. Sm is also known to suppress collagen-induced arthritis and in the current study we have found that the anti-arthritic effects of Sm were dependent on STAT6. The findings obtained in our research partially elucidated the anti-inflammatory effects of helminths and would contribute to development of lowly pathogenic helminth-based therapy on inflammatory diseases in the future.

Research Products

• [Journal Article] Reciprocal effects of Schistosoma mansoni infection on spontaneous autoimmune arthritis in IL-1 receptor antagonist-deficient mice (2015)
  • Author(s): Osada Y, Yamada S, Nakae S, Sudo K, Kanazawa T.
  • Journal Title: Parasitology International Volume: 64(1) Issue: 1 Pages: 13-17
  • DOI: 10.1016/j.parint.2014.09.001
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Involvement of IL-18 in the expansion of unique hepatic T cells with unconventional cytokine profiles during Schistosoma mansoni infection (2014)
  • Author(s): Keishi Adachi, Risa Nakamura, Yoshio Osada, Masachika Senba, Koji Tamada, Shinjiro Hamano
  • Journal Title: PLOS ONE Volume: 9 Issue: 5 Pages: e96042-e96042
  • DOI: 10.1371/journal.pone.0096042
  • NAID: 120006986559
  • Peer Reviewed / Open Access
• [Journal Article] Heligmosomoides polygyrus infection reduces severity of type 1 diabetes induced by multiple low-dose streptozotocin in mice via STAT6- and IL-10-independent mechanisms (2013)
  • Author(s): Osada Y, Yamada S, Nabeshima A, Yamagishi Y, Ishiwata K, Nakae S, Sudo K, Kanazawa T.
  • Journal Title: Experimental Parasitology Volume: 135 (2) Issue: 2 Pages: 388-396
  • DOI: 10.1016/j.exppara.2013.08.003
  • Peer Reviewed
• [Journal Article] Use of cell-free circulating schistosome DNA in serum, urine, semen, and saliva to monitor a case of refractory imported schistosomiasis hematobia (2013)
  • Author(s): Kato-Hayashi N, Yasuda M, Yuasa J, Isaka S, Haruki K, Ohmae H, Osada Y, Kanazawa T, Chigusa Y
  • Journal Title: J Clin Microbiol Volume: 51(10) Issue: 10 Pages: 3435-8
  • DOI: 10.1128/jcm.01219-13
  • Peer Reviewed
• [Journal Article] Unique T Cells with Unconventional Cytokine Profiles Induced in the Livers of Mice during Schistosoma mansoni Infection (2013)
  • Author(s): Keishi Adachi, Yoshio Osada, Risa Nakamura, Koji Tamada, Shinjiro Hamano
  • Journal Title: PLOS ONE Volume: 8 Issue: 12 Pages: e82698-e82698
  • DOI: 10.1371/journal.pone.0082698
  • NAID: 120006986731
  • Peer Reviewed
• [Presentation] STAT6やIL-10の欠損が住血吸虫による抗関節炎作用に及ぼす影響 (2016)
  • Author(s): 長田良雄、金澤保
  • Organizer: 第85回日本寄生虫学会大会
  • Place of Presentation: 宮崎市民プラザ（宮崎県宮崎市）
  • Year and Date: 2016-03-19
• [Presentation] 寄生蠕虫は宿主のIL-4, IL-10, IL-13シグナルが「同時に」欠損しても抗糖尿病効果を示す (2015)
  • Author(s): 長田良雄、金澤保
  • Organizer: 第68回日本寄生虫学会南日本支部大会・第65回日本衛生動物学会南日本支部大会 合同大会
  • Place of Presentation: 長崎大学医学部ポンペ会館（長崎県長崎市）
  • Year and Date: 2015-10-17
• [Presentation] 寄生蠕虫の抗糖尿病効果においてIL-4とIL-10は冗長的に関与しているのか？ (2015)
  • Author(s): 長田良雄、金澤保
  • Organizer: 第84 回日本寄生虫学会大会
  • Place of Presentation: 杏林大学三鷹キャンパス（東京都・三鷹市）
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] Helminths suppress streptozotocin-induced diabetes via STAT6- and IL-10-independent mechanisms (2014)
  • Author(s): Osada Y. Ishiwata K. Yamada S, Kanazawa T.
  • Organizer: 13th International Congress of Parasitology
  • Place of Presentation: ホテル・カミノレアル（メキシコ合衆国・メキシコシティ）
  • Year and Date: 2014-08-10 – 2014-08-15
• [Presentation] 寄生蠕虫感染が実験的自然発症関節炎に及ぼす影響 (2014)
  • Author(s): 長田良雄、中江進、須藤カツ子、金澤保
  • Organizer: 第35回日本炎症・再生医学会/第1回日本骨免疫会議
  • Place of Presentation: 万国津梁館（沖縄県・名護市）
  • Year and Date: 2014-07-01 – 2014-07-04
• [Presentation] 寄生蠕虫が実験的1型糖尿病マウスの遺伝子発現に及ぼす効果(続報) (2014)
  • Author(s): 長田良雄、加治つくし、神村直人、金澤保
  • Organizer: 第83回日本寄生虫学会大会
  • Place of Presentation: 愛媛大学城北キャンパス(松山)
• [Presentation] マンソン住血吸虫感染時にマウスの肝臓内で増加する、ユニークなサイトカイン産生能を有するＴ細胞集団について (2013)
  • Author(s): 安達圭志、長田良雄、中村梨沙、玉田耕治、濱野真二郎
  • Organizer: 第54回日本熱帯医学会大会
  • Place of Presentation: 長崎ブリックホール(長崎)
• [Presentation] マンソン住血吸虫感染がマウス自然発症関節炎に及ぼす相反的影響 (2013)
  • Author(s): 長田良雄、中江進、須藤カツ子、金澤保
  • Organizer: 第54回日本熱帯医学会大会
  • Place of Presentation: 長崎ブリックホール(長崎)
• [Presentation] マンソン住血吸虫感染がマウス自然発症関節炎に及ぼす相反的効果 (2013)
  • Author(s): 長田良雄、中江進、須藤カツ子、金澤保
  • Organizer: 第66 回日本寄生虫学会南日本支部大会
  • Place of Presentation: 大分大学医学部 臨床中講義室(大分)