Comprehensive studies on the contribution of CD147/basigin to Th cell differentiation and pathogenesis of psoriasis

• Project/Area Number: 18K08272
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Kagoshima University
• Principal Investigator: Kanekura Takuro 鹿児島大学, 医歯学域医学系, 教授 (70177509)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: CD147/Basigin / 乾癬 / 解糖系 / Th17細胞 / MCT / CD147/basigin / T細胞 / Th17

Outline of Final Research Achievements

Th17 plays an important role in psoriasis. The differentiation of naive CD4+ T-cells into Th17 cells depends on glycolysis as an energy source. CD147/Basigin regulates glycolysis in association with monocarboxylate transporters (MCT)-1 and - 4 in cancer- and T-cells. We examined whether CD147/Basigin is involved in the pathogenesis of psoriasis using samples from humans and psoriasis-model mice. The serum level of CD147 was increased in psoriasis patients and the expression of CD147 and MCT-1 was elevated on their dermal CD4+ RORγt+ T cells. In vitro, the potential of naive CD4+ T cells to differentiate into Th17 cells was abrogated in CD147-/- T-cells. Imiquimod (IMQ)-induced psoriatic dermatitis was significantly milder in CD147-/- mice and bone marrow chimeric mice lacking CD147 in hematopoietic cells of myeloid lineage. These findings demonstrate that CD147 is essential for the development of psoriasis via the induction of Th17 cell differentiation.

Academic Significance and Societal Importance of the Research Achievements

CD147/basiginは申請者ら自身がクローニングした分子であり、CD147/basiginとT細胞の分化機構の観点から乾癬の病態を包括的に解明したもので学術的に極めて先駆的かつ独創的なものである。近年乾癬治療に用いられる生物学的製剤はTh17細胞が産生するIL-17やTh17を活性化するIL-23をターゲットとしているのに対して、Th17細胞への分化を制御するより根本的な治療の開発につながる成果であり社会的意義が大きい。またTh17細胞関連疾患には乾癬以外にも多くの疾患が含まれるので本研究の意義は皮膚科領域にとどまらず学際的で重要性の高いものである。

Research Products

• [Journal Article] Therapeutic Efficacy of Etretinate on Cutaneous-type Adult T-cell Leukemia-Lymphoma (2019)
  • Author(s): Yonekura K、Takeda K、Kawakami N、Kanzaki T、Kanekura T、Utsunomiya A
  • Journal Title: Acta Dermato Venereologica Volume: 99 Issue: 9 Pages: 774-776
  • DOI: 10.2340/00015555-3196
  • Peer Reviewed
• [Journal Article] E-cadherin loss in RMG-1?cells inhibits cell migration and its regulation by Rho GTPases (2019)
  • Author(s): Haraguchi Misako、Fukushige Tomoko、Kanekura Takuro、Ozawa Masayuki
  • Journal Title: Biochemistry and Biophysics Reports Volume: 18 Pages: 100650-100650
  • DOI: 10.1016/j.bbrep.2019.100650
  • Peer Reviewed / Open Access
• [Journal Article] Numbers of forkhead box P3‐positive cells and programmed cell death 1‐positive cells were associated with spontaneous regression in a patient with primary cutaneous diffuse large B‐cell lymphoma with multiple lesions (2019)
  • Author(s): Fujii Kazuyasu、Uchida Youhei、Hatanaka Miho、Jimura Nozomi、Okubo Aoi、Sakanoue Masanao、Higashi Yuko、Kawabata Hisashi、Kanekura Takuro
  • Journal Title: The Journal of Dermatology Volume: 46 Issue: 11
  • DOI: 10.1111/1346-8138.14948
  • Peer Reviewed
• [Journal Article] Application of high-mannose-type glycan-specific lectin from Oscillatoria Agardhii for affinity isolation of tumor-derived extracellular vesicles (2019)
  • Author(s): Yamamoto Mika、Harada Yoichiro、Suzuki Takehiro、Fukushige Tomoko、Yamakuchi Munekazu、Kanekura Takuro、Dohmae Naoshi、Hori Kanji、Maruyama Ikuro
  • Journal Title: Analytical Biochemistry Volume: 580 Pages: 21-29
  • DOI: 10.1016/j.ab.2019.06.001
  • Peer Reviewed
• [Journal Article] Prominent Dermal Langerhans Cells in an Omenn Syndrome Patient With a Novel Mutation in the IL2RG Gene (2019)
  • Author(s): Ibusuki Atsuko、Nishikawa Takuro、Hiraki Tsubasa、Okano Tsubasa、Imai Kohsuke、Kanegane Hirokazu、Ohnishi Hidenori、Kato Zenichiro、Fujii Kazuyasu、Tanimoto Akihide、Kawano Yoshifumi、Kanekura Takuro
  • Journal Title: The Journal of Dermatology Volume: 46 Issue: 11 Pages: 1019-1023
  • DOI: 10.1111/1346-8138.15054
  • Peer Reviewed / Open Access
• [Journal Article] Granulomatous/sarcoid‐like reactions in the setting of programmed cell death‐1 inhibition: a potential mimic of disease recurrence (2019)
  • Author(s): Hiraki Tsubasa、Hatanaka Miho、Arimura Akiko、Kawahira Hisao、Kirishima Mari、Kitazono Ikumi、Horinouchi Michiko、Higashi Michiyo、Kanekura Takuro、Tanimoto Akihide
  • Journal Title: Journal of Cutaneous Pathology Volume: 47 Issue: 2 Pages: 154-160
  • DOI: 10.1111/cup.13569
  • Peer Reviewed
• [Journal Article] Novel AP3B1 compound heterozygous mutations in a Japanese patient with Hermansky?Pudlak syndrome type 2 (2019)
  • Author(s): Nishikawa Takuro、Okamura Ken、Moriyama Mizuki、Watanabe Kenji、Ibusuki Atsuko、Sameshima Seiji、Masamoto Izumi、Yamazaki Ieharu、Tanita Kay、Kanekura Takuro、Kanegane Hirokazu、Suzuki Tamio、Kawano Yoshifumi
  • Journal Title: The Journal of Dermatology Volume: 47 Issue: 2 Pages: 185-189
  • DOI: 10.1111/1346-8138.15177
  • Peer Reviewed / Open Access
• [Journal Article] Silk fibroin produced by transgenic silkworms overexpressing the Arg-Gly-Asp motif accelerates cutaneous wound healing in mice. (2019)
  • Author(s): Baba A, Matsushita S, Kitayama K, Asakura T, Sezutsu H, Tanimoto A, Kanekura T.
  • Journal Title: J Biomed Mater Res Part B Volume: 107 Pages: 97-103
  • Peer Reviewed
• [Journal Article] The Association of Peroxiredoxin 4 with the Initiation and Progression of Hepatocellular Carcinoma. (2019)
  • Author(s): Guo X, Nocuchi H, Ishii N, Homma T, Hamada T, Hiraki T, Zhang J, Matsuo K, Yokoyama S, Ishibashai H, Fukushige T, Kanekura T, Fujii J, Uramoto H, Tanimoto A, Yamada S.
  • Journal Title: Antioxid Redox Signal Volume: 30 Pages: 1271-1284
  • Peer Reviewed
• [Journal Article] Generation of the heterogeneity of extracellular vesicles by membrane organization and sorting machineries. (2019)
  • Author(s): Harada Y, Suzuki T, Fukushige T, Kizuka Y, Yagi H, Yamamoto M, Kondo K, Inoue H, Kato K, Taniguchi N, Kanekura T, Dohmae N, Maruyama I.
  • Journal Title: Biochim Biophys Acta - Gen Subjects Volume: 1863 Pages: 681-691
  • Peer Reviewed
• [Journal Article] Clinical and immunological effects of adsorptive myeloid lineage leucocyte apheresis in patients with immune disorders. (2018)
  • Author(s): Kanekura T.
  • Journal Title: J Dermatol Volume: 45 Issue: 8 Pages: 945-950
  • DOI: 10.1111/1346-8138.14471
  • Peer Reviewed
• [Journal Article] All-trans retinoic acid induces CD4+CD25+FoxP3+ regulatory T cells by increasing FoxP3 demethylation in systemic sclerosis CD4+ T cells. (2018)
  • Author(s): Sun X, Xiao Y, Zeng Z, Shi Y, Tang B, Long H, Kanekura T, Wang J, Wu H, Zhao M, Lu Q, Xiao R.
  • Journal Title: J Immunol Res Volume: 30
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Japanese Guidelines for the Management and Treatment of Generalized Pustular Psoriasis. (2018)
  • Author(s): Fujita H, Terui T, Hayama K, Akiyama M, Ikeda S, Mabuchi T, Ozawa A, Kanekura T, Kurosawa M, Komine M, Nakajima K, Sano S, Nemoto O, Muto M, Imai Y, Yamanishi K, Aoyama Y, Iwatsuki K.
  • Journal Title: J Dermatol Volume: 45 Pages: 1235-1270
  • Peer Reviewed
• [Journal Article] Comparison of oxidative stress on DNA, protein, and lipid in patients with actinic keratosis, Bowen’s disease, and squamous cell carcinoma. (2018)
  • Author(s): Yoshifuku A, Fujii K, Kanekura T.
  • Journal Title: J Dermatol Volume: 45 Pages: 1319-1323
  • Peer Reviewed
• [Journal Article] Cross-sectional survey on disease severity in Japanese patients with harlequin ichthyosis/ichthyosis: Syndromic forms and quality-of-life analysis in a subgroup. (2018)
  • Author(s): Murase C, Takeuchi T, Shibata A, Nakatochi M, Kinoshita F, Kubo A, Nakajima K, Ishii N, Amano H, Masuda K, Kawakami H, Kanekura T, Washio K, Asano M, Teramura K, Akasaka E, Tohyama M, Hatano Y, Ochiai T, Moriwaki S, Sato T, Ishida-Yamamoto A, Seishima M, Kurosawa M, Ikeda S, Akiyama M.
  • Journal Title: J Dermatol Sci Volume: 92 Pages: 127-133
  • NAID: 120006623824
  • Peer Reviewed
• [Presentation] CD147/Basigin はTh17細胞への分化を制御し乾癬の病態形成に関与する (2021)
  • Author(s): 大久保葵，内田洋平，東 裕子，龍華章裕，門松健治，金蔵拓郎
  • Organizer: 第14回桜ケ丘地区基礎系研究発表会
• [Presentation] CD147/Basigin regulates Th17 cell differentiation and contributes to the pathogenesis of psoriasis. (2020)
  • Author(s): Aoi Okubo, Youhei Uchida, Yuko Higashi, Akihiro Ryuge, Kenji Kadomatsu, Takuro Kanekura
  • Organizer: The 45th Annual Meeting of the Japanese Society for Investigative Dermatology
• [Presentation] 膿疱性乾癬の新たな治療 (2018)
  • Author(s): 金蔵拓郎
  • Organizer: 皮膚疾患 Clinical Conference
  • Invited