Possible role of KIR2DL4 on human decidual mast cells in pregnancy

• Project/Area Number: 18K07014
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Iwate Medical University (2020); Kyoto University (2018-2019)
• Principal Investigator: Kataoka Tatsuki 岩手医科大学, 医学部, 教授 (20343254)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: マスト細胞 / 妊娠成立 / 不妊症 / 脱落膜 / 妊娠 / 不妊 / 卵管妊娠 / LIF / トロホブラスト / KIR2DL4 / HLA-G

Outline of Final Research Achievements

We found that all human decidual mast cells and a human mast cell line LAD2 expressed KIR2DL4, and that these cells produced LIF and MMP-9 by stimulating a KIR2DL4 ligand HLA-G. We also found that LIF derived from LAD2 enhanced the migration of a human trophoblast cell line HTR-8/SVneo, and MMP-9 derived from LAD2 enhanced tube formation of HTR-8/SVneo.
In addition, decidual mast cells diminished or significantly decreased in number and KIR2DL4 expression in infertile patients with long-term corticosteroid treatment.
Thus, we show the involvement of human decidual mast cell in pregnancy, and possible involvement of mast cell abnormality in some infertility.

Academic Significance and Societal Importance of the Research Achievements

マスト細胞が妊娠成立に関わることについて、分子生物学的結果を持って証明したのは我々が世界初である。アレルギー症状を引き起こすマスト細胞の持つ本来の生理的役割を明らかにしたという点で科学的意義があるといえる。
そして、不妊の一部にマスト細胞異常が関わっていることも見出しており、これは不妊症の診断にマスト細胞が使えることを示していると同時に、この細胞が不妊症の治療標的となる可能性も示すものと考えている。

Research Products

• [Journal Article] Temporal triangular alopecia confined to the frontal scalp. (2021)
  • Author(s): Tahara J, Dainichi T, Kaku Y, Kataoka T, Kishimoto H, Kogame T, Kabashima K.
  • Journal Title: J Dermatol Volume: 48 Issue: 4
  • DOI: 10.1111/1346-8138.15776
  • Peer Reviewed / Open Access
• [Journal Article] Neonatal Fc receptor induces intravenous immunoglobulin growth suppression in Langerhans cell histiocytosis (2021)
  • Author(s): Nabeshima Y, Kataoka TR, Ueshima C, Saito N, Hirata M, Takeuchi Y, Takei Y, Moriyoshi K, Ono K, Haga H.
  • Journal Title: Pathol Int Volume: 71 Issue: 3 Pages: 191-197
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• [Journal Article] A case of Langerhans cell sarcoma on the scalp: Whole-exome sequencing reveals a role of ultraviolet in the pathogenesis (2021)
  • Author(s): Katsuragawa H, Yamada Y, Ishida Y, Kaku Y, Fujimoto M, Kataoka TR, Haga H.
  • Journal Title: Pathol Int Volume: 70 Issue: 11 Pages: 881-887
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  • NAID: 120006898145
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• [Journal Article] Unbiased Detection of Driver Mutations in Extramammary Paget Disease (2020)
  • Author(s): Ishida Yoshihiro、Ogawa Seishi et al.
  • Journal Title: Clinical Cancer Research Volume: 27 Issue: 6 Pages: 1756-1765
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• [Journal Article] Downregulated ATP6V1B1 expression acidifies the intracellular environment of cancer cells leading to resistance to antibody-dependent cellular cytotoxicity (2020)
  • Author(s): Nishie Mariko、Suzuki Eiji、Hattori Masakazu、Kawaguch Kosuke、Kataoka Tatsuki R.、Hirata Masahiro、Pu Fengling、Kotake Takeshi、Tsuda Moe、Yamaguchi Ayane、Sugie Tomoharu、Toi Masakazu
  • Journal Title: Cancer Immunology, Immunotherapy Volume: 70 Issue: 3 Pages: 817-830
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• [Journal Article] Perihilar cholangiocarcinoma in an explanted liver after Kasai operation for biliary atresia: A case report and literature review (2020)
  • Author(s): Uno Shunsuke、Kataoka Tatsuki R.、Okajima Hideaki、Taura Kojiro、Sakurai Takaki、Haga Hironori
  • Journal Title: Pathology International Volume: 70 Issue: 11 Pages: 888-892
  • DOI: 10.1111/pin.13016
• [Journal Article] Upregulated programmed death ligand 1 expression in nivolumab‐induced lichen nitidus: A follow‐up report with an immunohistochemical analysis (2020)
  • Author(s): Komatsu‐Fujii Takayoshi、Nakajima Saeko、Iwata Masashi、Kataoka Tatsuki、Hirata Masahiro、Nomura Takashi、Kabashima Kenji
  • Journal Title: The Journal of Dermatology Volume: 47 Issue: 9
  • DOI: 10.1111/1346-8138.15480
• [Journal Article] Uterine cervical squamous cell carcinoma without p16 (CDKN2A) expression: Heterogeneous causes of an unusual immunophenotype (2020)
  • Author(s): Rokutan‐Kurata Mariyo、Minamiguchi Sachiko、Kataoka Tatsuki R、Abiko Kaoru、Mandai Masaki、Haga Hironori
  • Journal Title: Pathology International Volume: 70 Issue: 7 Pages: 413-421
  • DOI: 10.1111/pin.12930
  • NAID: 120006885398
• [Journal Article] IGF2BP3 (IMP3) expression in angiosarcoma, epithelioid hemangioendothelioma, and benign vascular lesions (2020)
  • Author(s): Okabayshi Misuzu、Kataoka Tatsuki R.、Oji Marina、Mibayashi Satoko、Odani Kentaro、Otsuka Atsushi、Haga Hironori
  • Journal Title: Diagnostic Pathology Volume: 15 Issue: 1 Pages: 26-26
  • DOI: 10.1186/s13000-020-00951-x
• [Journal Article] SLAM family member 8 is expressed in and enhances the growth of anaplastic large cell lymphoma. (2020)
  • Author(s): Sugimoto A, Kataoka TR, Ito H, Kitamura K, Saito N, Hirata M, Ueshima C, Takei Y, Moriyoshi K, Otsuka Y, Nishikori M, Takaori-Kondo A, Haga H.
  • Journal Title: Sci Rep. Volume: 10 Issue: 1 Pages: 2505-2505
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  • NAID: 120006895429
  • Peer Reviewed / Open Access
• [Journal Article] Killer Immunoglobulin-Like Receptor 2DL4 (CD158d) Regulates Human Mast Cells both Positively and Negatively: Possible Roles in Pregnancy and Cancer Metastasis. (2020)
  • Author(s): Kataoka TR, Ueshima C, Hirata M, Minamiguchi S, Haga H.
  • Journal Title: Int J Mol Sci. Volume: 21 Issue: 3 Pages: 954-954
  • DOI: 10.3390/ijms21030954
  • NAID: 120006796471
  • Peer Reviewed / Open Access
• [Journal Article] A randomized, 3-arm, neoadjuvant, phase 2 study comparing docetaxel + carboplatin + trastuzumab + pertuzumab (TCbHP), TCbHP followed by trastuzumab emtansine and pertuzumab (T-DM1+P), and T-DM1+P in HER2-positive primary breast cancer. (2020)
  • Author(s): Masuda N, Ohtani S, Takano T, Inoue K, Suzuki E, Nakamura R, Bando H, Ito Y, Ishida K, Yamanaka T, Kuroi K, Yasojima H, Kasai H, Takasuka T, Sakurai T, Kataoka TR, Morita S, Ohno S, Toi M.
  • Journal Title: Breast Cancer Res Treat. Volume: 180 Issue: 1 Pages: 135-146
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• [Journal Article] High-resolution imaging mass spectrometry combined with transcriptomic analysis identified a link between fatty acid composition of phosphatidylinositols and the immune checkpoint pathway at the primary tumour site of breast cancer. (2020)
  • Author(s): Kawashima M, Tokiwa M, Nishimura T, Kawata Y, Sugimoto M, Kataoka TR, Sakurai T, Iwaisako K, Suzuki E, Hagiwara M, Harris AL, Toi M.
  • Journal Title: Br J Cancer. Volume: 122 Issue: 2 Pages: 245-257
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  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A case of renal cell carcinoma unclassified with medullary phenotype without detectable gene deletion. (2019)
  • Author(s): Tsuzuki S, Kataoka TR, Ito H, Ueshima C, Asai S, Yokoo H, Haga H.
  • Journal Title: Pathol Int. Volume: 69 Issue: 12 Pages: 710-714
  • DOI: 10.1111/pin.12858
  • Peer Reviewed / Open Access
• [Journal Article] Variable indoleamine 2,3-dioxygenase expression in acral/mucosal melanoma and its possible link to immunotherapy. (2019)
  • Author(s): Iga N, Otsuka A, Hirata M, Kataoka TR, Irie H, Nakashima C, Matsushita S, Uchi H, Yamamoto Y, Funakoshi T, Fujisawa Y, Yoshino K, Fujimura T, Hata H, Ishida Y, Kabashima K.
  • Journal Title: Cancer Sci. Volume: 110 Issue: 11 Pages: 3434-3441
  • DOI: 10.1111/cas.14195
  • NAID: 120006878517
  • Peer Reviewed / Open Access
• [Journal Article] Diffuse hair loss following anti-programmed cell death-1 antibody treatment: a case report with immunohistochemical analysis. (2019)
  • Author(s): Komatsu-Fujii T, Otsuka A, Ishida Y, Kaku Y, Yamashita C, Hata A, Kataoka T, Honda T, Kabashima K.
  • Journal Title: Eur J Dermatol. Volume: 29 Pages: 326-327
  • Peer Reviewed / Open Access
• [Journal Article] Alteration of specific cytokine expression patterns in patients with breast cancer. (2019)
  • Author(s): Kawaguchi K, Sakurai M, Yamamoto Y, Suzuki E, Tsuda M, Kataoka TR, Hirata M, Nishie M, Nojiri T, Kumazoe M, Saito K, Toi M.
  • Journal Title: Sci Rep. Volume: 9 Issue: 1 Pages: 2924-2924
  • DOI: 10.1038/s41598-019-39476-9
  • NAID: 120006578938
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• [Journal Article] Primary small bowel mesentery de-differentiated liposarcoma causing torsion with no recurrence for 5 years: A case report and review of the literature. (2018)
  • Author(s): Matsuo K, Inoue M, Shirai Y, Kataoka T, Kagota S, Taniguchi K, Lee SW, Uchiyama K.
  • Journal Title: Medicine (Baltimore). Volume: 97 Issue: 48 Pages: e13446-e13446
  • DOI: 10.1097/md.0000000000013446
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• [Journal Article] Histopathological characterization of the neuroglial tissue in ovarian teratoma associated with anti-N-methyl-D-aspartate (NMDA) receptor encephalitis. (2018)
  • Author(s): Iemura Y, Yamada Y, Hirata M, Kataoka TR, Minamiguchi S, Haga H.
  • Journal Title: Pathol Int. Volume: 68 Issue: 12 Pages: 677-684
  • DOI: 10.1111/pin.12732
  • Peer Reviewed / Open Access
• [Journal Article] A case of possible chemical leukoderma secondary to usage of skin whitening agents. (2018)
  • Author(s): Cho M, Otsuka A, Irie H, Kataoka T, Kabashima K.
  • Journal Title: Eur J Dermatol. Volume: 28 Pages: 701-702
  • Peer Reviewed / Open Access
• [Journal Article] Multiple Polypoid Lesions in the Ileum After Treatment for Primary Ileal Follicular Lymphoma. (2018)
  • Author(s): Kitamoto H, Kataoka T, Yamamoto S.
  • Journal Title: Gastroenterology. Volume: 156 Issue: 3 Pages: 552-553
  • DOI: 10.1053/j.gastro.2018.08.048
  • Peer Reviewed / Open Access
• [Journal Article] A Case of Pityriasis Rubra Pilaris Treated Successfully with the Phosphodiesterase-4 Inhibitor Apremilast. (2018)
  • Author(s): Cho M, Honda T, Ueshima C, Kataoka T, Otsuka A, Kabashima K.
  • Journal Title: Acta Derm Venereol. Volume: 98 Issue: 10 Pages: 975-976
  • DOI: 10.2340/00015555-2995
  • NAID: 120006539576
  • Peer Reviewed / Open Access
• [Journal Article] A rare case of primary small bowel de-differentiated liposarcoma causing intussusception: A case report. (2018)
  • Author(s): Matsuo K, Inoue M, Shirai Y, Kataoka T, Kagota S, Taniguchi K, Lee SW, Uchiyama K.
  • Journal Title: Medicine (Baltimore). Volume: 97 Issue: 24 Pages: e11069-e11069
  • DOI: 10.1097/md.0000000000011069
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of possible structures of inducible skin-associated lymphoid tissue in lupus erythematosus profundus. (2018)
  • Author(s): Kogame T, Yamashita R, Hirata M, Kataoka TR, Kamido H, Ueshima C, Matsui M, Nomura T, Kabashima K.
  • Journal Title: J Dermatol. Volume: 45 Issue: 9 Pages: 1117-1121
  • DOI: 10.1111/1346-8138.14498
  • Peer Reviewed / Open Access
• [Journal Article] RUNX1 positively regulates the ErbB2/HER2 signaling pathway through modulating SOS1 expression in gastric cancer cells. (2018)
  • Author(s): Mitsuda Y, Morita K, Kashiwazaki G, Taniguchi J, Bando T, Obara M, Hirata M, Kataoka TR, Muto M, Kaneda Y, Nakahata T, Liu PP, Adachi S, Sugiyama H, Kamikubo Y.
  • Journal Title: Sci. Rep. Volume: 8 Issue: 1 Pages: 6423-6423
  • DOI: 10.1038/s41598-018-24969-w
  • NAID: 120006510275
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Angiolymphoid hyperplasia with eosinophilia: A case of spontaneous partial regression post-biopsy. (2018)
  • Author(s): Cho M, Kaku Y, Goto K, Endo Y, Kataoka T, Otsuka A, Kabashima K.
  • Journal Title: J Dermatol. Volume: 45 Issue: 10
  • DOI: 10.1111/1346-8138.14306
  • Peer Reviewed / Open Access
• [Journal Article] Possible Involvement of Human Mast Cells in the Establishment of Pregnancy via Killer Cell Ig-Like Receptor 2DL4. (2018)
  • Author(s): Ueshima C, Kataoka TR, Hirata M, Sugimoto A, Iemura Y, Minamiguchi S, Nomura T, Haga H.
  • Journal Title: Am J Pathol. Volume: 188 Issue: 6 Pages: 1497-1508
  • DOI: 10.1016/j.ajpath.2018.02.012
  • Peer Reviewed