New mechanism of autoimmune diseases mediated by misfolded protein/MHC class II complex
| Project/Area Number |
15H02545
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | Osaka University |
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Principal Investigator |
Arase Hisashi 大阪大学, 微生物病研究所, 教授 (10261900)
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| Co-Investigator(Kenkyū-buntansha) |
末永 忠広 大阪大学, 微生物病研究所, 准教授 (20396675)
平安 恒幸 金沢大学, 先進予防医学研究センター, 特任准教授 (30585170)
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| Research Collaborator |
ISE Masako (KOHYAMA Masako)
KUMANOGO Atsushi
KATAYAMA Ichiro
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥41,470,000 (Direct Cost: ¥31,900,000、Indirect Cost: ¥9,570,000)
Fiscal Year 2017: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2016: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2015: ¥14,430,000 (Direct Cost: ¥11,100,000、Indirect Cost: ¥3,330,000)
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| Keywords | 自己免疫疾患 / 自己抗体 / MHC / ミスフォールド蛋白質 |
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| Outline of Final Research Achievements |
We found that autoantibodies that cannot be detected by general laboratory test can be detected using misfolded protein-HLA class II complex. MPO-HLA class II complex was found to be involved in ANCA-associated vasculitis as a target for autoantibodies. IgG/HLA class II complex generated in rheumatoid arthritis was found to be a ligand for FcγRIII expressed on NK cells, which is involved in the activation of NK cells in rheumatoid arthritis. These studies revealed that misfolded proteins complexed with HLA class II molecules play an important role in the pathogenesis of autoimmune diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の結果、自己抗原・HLAクラスII複合体を用いると従来方法で検出できなかった抗原特異性の自己抗体が検出できるようになることが判明した。また、自己抗原・HLAクラスII複合体は異所性に発現したHLAクラスII分子によって形成されると考えられる。異所性HLAクラスII発現阻害剤は、サイトカインシグナル全般を抑制するJAK阻害剤等に比べて作用点が限られており、感染症等の副作用の少ない新たなタイプの免疫制御薬となることが期待できることが判明した。これらの成果は、自己免疫疾患の新たな診断法、治療薬の開発に重要であると考えられる。
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Report
(4 results)
Research Products
(78 results)
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[Journal Article] Blocking immunoinhibitory receptor LILRB2 reprograms tumor-associated myeloid cells and promotes antitumor immunity.2018
Author(s)
Chen HM, van der Touw W, Wang YS, Kang K, Mai S, Zhang J, Alsina-Beauchamp D, Duty JA, Mungamuri SK, Zhang B, Moran T, Flavell R, Aaronson S, Hu HM, Arase H, Ramanathan S, Flores R, Pan PY, Chen SH.
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Journal Title
J. Clin. Invest.
Volume: 128
Issue: 12
Pages: 5647-5662
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration.2018
Author(s)
Deng M, 外30名, Arase H, Xia N, Jiang Y, Collins R, You MJ, Homsi J, Unni N, Lewis C, Chen GQ, Fu YX, Liao XC, An Z, Zheng J, Zhang N, Zhang CC.
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Journal Title
Nature.
Volume: 562
Issue: 7728
Pages: 605-609
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Heme ameliorates dextran sodium sulfate-induced colitis through providing intestinal macrophages with noninflammatory profiles.2018
Author(s)
Kayama H, Kohyama M, Okuzaki D, Motooka D, Barman S, Okumura R, Muneta M, Hoshino K, Sasaki I, Ise W, Matsuno H, Nishimura J, Kurosaki T, Nakamura S, Arase H, Kaisho T, Takeda K.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 115
Issue: 33
Pages: 8418-8423
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Novel autoantibody against the β2-glycoprotein I/HLA-DR complex in patients with refractory cutaneous ulcers2017
Author(s)
Arase N, Tanimura K, Jin H, Yamaoka T, Kishibe M, Nishioka M, Kiyohara E, Tani M, Matsuoka S, Ohmura K, Takasugi K, Yamamoto T, Murota H, Arase H, Katayama I.
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Journal Title
Br J Dermatol.
Volume: 印刷中
Issue: 1
Pages: 272-275
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors2017
Author(s)
Saito Fumiji、Hirayasu Kouyuki、Satoh Takeshi、Wang Christian W.、Lusingu John、Arimori Takao、Shida Kyoko、Palacpac Nirianne Marie Q.、Itagaki Sawako、Iwanaga Shiroh、Takashima Eizo、Tsuboi Takafumi、Kohyama Masako、Suenaga Tadahiro、Colonna Marco、Takagi Junichi、Lavstsen Thomas、Horii Toshihiro、Arase Hisashi
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Journal Title
Nature.
Volume: 552
Issue: 7683
Pages: 101-105
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] LILRA2 is an innate immune sensor for microbially cleaved immunoglobulins.2016
Author(s)
Hirayasu K, Saito F, Suenaga T, Shida K, Arase N, Oikawa K, Yamaoka T, Murota H, Chibana H, Nagai H, Nakamura Y, Katayama I, Colonna M, Arase H.
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Journal Title
Nature Microbiology
Volume: -
Issue: 6
Pages: 1-7
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That Directly Induces Lymphoma Cell Death via Large Pore Formation.2016
Author(s)
Matsuoka S, Ishii Y, Nakao A, Abe M, Ohtsuji N, Momose S, Jin H, Arase H, Sugimoto K, Nakauchi Y, Masutani H, Maeda M, Yagita H, Komatsu N, Hino O
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Journal Title
PLoS One
Volume: 11
Issue: 3
Pages: e0150496-e0150496
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] Antiphospholipid antibody recognizes β2GPI complexed with HLA class II molecules via its domain V2017
Author(s)
Yuki Sasagawa, Kenji Tanimura, Hui Jin, Noriko Arase, Tadahiro Suenaga, Masako Kohyama, Kouyuki Hirayasu, Satoko Morikami, Yasuhiko Ebina, Tatsuya Atsumi, Hideto Yamada, Hisashi Arase
Organizer
第46回日本免疫学会学術集会
Related Report
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[Presentation] Myeloperoxidase/HLA class II complexes are targets for autoantibodies in ANCA-associated vasculitis2015
Author(s)
Hiwa Ryosuke, Ohmura Koichiro, Arase Noriko, Jin Hui, Hirayasu Kouyuki, Kohayama Masako, Suenaga Tadahiro, Saito Fumiji, Iwatani Hirotsugu, Atsumi Tatsuya, Terao Chikashi, Mimori Tsuneyo, Arase Hisashi
Organizer
第44日本免疫学会学術集会
Place of Presentation
札幌コンベンションセンター（北海道）
Year and Date
2015-11-18
Related Report
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[Presentation] MPO/HLA classⅡ複合体は顕微鏡的多発血管炎における自己抗体の標的である2015
Author(s)
日和良介, 大村浩一郎, 荒瀬規子, 金暉, 平安恒幸, 香山雅子, 末永忠広, 齋藤史路, 岩谷博次, 渥美達也, 寺尾知可史, 三森経世, 荒瀬尚
Organizer
第43回日本臨床免疫学会総会
Place of Presentation
神戸国際会議場(兵庫）
Year and Date
2015-10-22
Related Report
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