Papers - Kurebayashi, Yutaka

Imiquimod-induced dermatitis impairs thymic tolerance of autoreactive CD4⁺ T cells to desmoglein 3

Iriki H., Mukai M., Ito H., Kurebayashi Y., Amagai M., Takahashi H.

Journal of Dermatological Science (Journal of Dermatological Science)  100 ( 3 ) 166 - 174 2020

ISSN  09231811

　View Summary

© 2020 Japanese Society for Investigative Dermatology Background: The thymus plays an essential role in removing autoreactive T cells. Autoantigen-expressing thymic epithelial cells (TECs) contribute to the tolerogenic process. The thymus transiently shrinks as an acute thymic involution (ATI) under various inflammatory conditions. However, whether ATI occurs during local skin inflammation remains unclear, as does its influence on thymic immune tolerance. Objective: We investigated whether imiquimod-induced dermatitis causes ATI and impairs thymic immune tolerance against desmoglein 3 (Dsg3), an epidermal autoantigen of pemphigus vulgaris. Methods: 5% imiquimod cream was applied daily, at 62.5 mg/day (high dose group) or 31.25 mg/day (low dose group), for 1 week on the back of wild-type mice, and to wild-type mice that had undergone bone-marrow transplantation from Dsg3-specific T-cell receptor (TCR) transgenic-Rag2−/− mice. Next, thymocytes, TECs and other immune cells were analyzed by flow cytometry. TEC-associated Dsg3 expression was also analyzed by immunofluorescence staining. Results: Thymus weight and thymocyte number in all developmental stages decreased in a dose-dependent manner under imiquimod-induced dermatitis. The number of total TECs, specifically medullary, but not cortical, TECs, decreased in high and low dose groups. Accordingly, the number of Dsg3-experssing UEA-1+keratin 5+mTEC decreased in the thymus during imiquimod-induced dermatitis. Although Dsg3-sepcific transgenic thymocytes was usually deleted in the thymus under physiological condition by central tolerance, Dsg3-sepcific transgenic CD4+CD8− thymocytes significantly increased in number under imiquimod-induced dermatitis. Conclusion: These findings indicate a crosstalk between skin and thymus in adult mice and suggest that skin inflammation may impair thymic tolerance to autoantigens, such as Dsg3.

• Access to Document (DOI)

IL-6 and G-CSF production resulting from lung cancer in an HIV patient

Kawakami N., Namkoong H., Masaki K., Kurebayashi Y., Shimoda M., Kotani H., Fujiwara H., Hasegawa N.

IDCases (IDCases)  19   e00693 2020

ISSN  22142509

　View Summary

© 2020 Increasing reports have noted an increased prevalence of lung cancer in human immunodeficiency virus (HIV)-positive patients with poor prognosis. A 51-year-old HIV-positive man was diagnosed with stage IV squamous cell lung cancer. He had high grade spike intermittent fever and persistent elevation of the white blood cell count as well as C-reactive protein (CRP) levels. Although we suspected opportunistic infections, we did not detect any infection. The autopsy showed positive immunostaining for Interleukin-6 (IL-6) in plasma cells of the stromal regions and G-CSF in tumor cells, which were considered responsible for his significant tumor fever, leukocytosis and high titers of CRP. This case report highlights the need to consider cytokine-producing tumor as a differential diagnosis of fever and high inflammatory status in HIV-positive cancer patients.

• Access to Document (DOI)

Contiguous Metastasis of Pulmonary Adenocarcinoma to Meningioma

Nakaya M., Ichimura S., Kurebayashi Y., Mochizuki Y., Fukaya R., Fukuchi M., Fujii K.

Journal of Neurological Surgery, Part A: Central European Neurosurgery (Journal of Neurological Surgery, Part A: Central European Neurosurgery)  80 ( 2 ) 127 - 130 2019

ISSN  21936315

　View Summary

© 2019 Georg Thieme. All rights reserved. Background Metastasis from one tumor into another is known as tumor-to-tumor metastasis. We report a case of a contiguous occurrence of meningioma and brain cancer metastasis. Patient A 91-year-old woman presented with a sudden onset of weakness in her right limbs and gait disturbance. Fourteen years previously, she had a tumor that was suspected to be a meningioma in the left frontal convexity with no change for several years. One year earlier to presentation she was diagnosed with lung carcinoma in the left lower lobe. Results Magnetic resonance images revealed enlargement of the tumor with perifocal edema. Histologic examination showed a meningioma with contiguous metastatic poorly differentiated adenocarcinoma, as well as a clearly defined border between the two components. The clinical origin of the metastasis was presumed to be from the left lower lobe of the lung. Conclusion Although our case does not strictly fulfill the definition of tumor-to-tumor metastasis, we suggest a contiguous occurrence develops by the same mechanism and may be a subtype of this process. Although previous reports suggested the loss of epithelial cadherin (E-cadherin) expression in the recipient tumor as the cause of contiguous metastasis, E-cadherin expression was positive in our case and did not seem to be involved in the localization of the metastasis.

• Access to Document (DOI)

Brain metastasis from urachal carcinoma.

Takahara K, Mochizuki Y, Ichimura S, Kurebayashi Y, Fujii K

Surgical neurology international 10   152 2019

ISSN  2229-5097

• Access to Document (DOI)

Landscape of immune microenvironment in hepatocellular carcinoma and its additional impact on histological and molecular classification

Kurebayashi Y., Ojima H., Tsujikawa H., Kubota N., Maehara J., Abe Y., Kitago M., Shinoda M., Kitagawa Y., Sakamoto M.

Hepatology (Hepatology)  68 ( 3 ) 1025 - 1041 2018.09

ISSN  02709139

　View Summary

© 2018 by the American Association for the Study of Liver Diseases. Immune cells constitute an important element of tumor tissue. Accumulating evidence indicates their clinicopathological significance in predicting prognosis and therapeutic efficacy. Nonetheless, the combinations of immune cells forming the immune microenvironment and their association with histological findings remain largely unknown. Moreover, it is unclear which immune cells or immune microenvironments are the most prognostically significant. Here, we comprehensively analyzed the immune microenvironment and its intratumor heterogeneity in 919 regions of 158 hepatocellular carcinomas (HCCs), and the results were compared with the corresponding histological and prognostic data. Consequently, we classified the immune microenvironment of HCC into three distinct immunosubtypes: Immune-high, Immune-mid, and Immune-low. The Immune-high subtype was characterized by increased B-/plasma-cell and T cell infiltration, and the Immune-high subtype and B-cell infiltration were identified as independent positive prognostic factors. Varying degrees of intratumor heterogeneity of the immune microenvironment were observed, some of which reflected the multistep nature of HCC carcinogenesis. However, the predominant pattern of immunosubtype and immune cell infiltration of each tumor was prognostically important. Of note, the Immune-high subtype was associated with poorly differentiated HCC, cytokeratin 19 (CK19)+, and/or Sal-like protein 4 (SALL4)+ high-grade HCC, and Hoshida's S1/Boyault's G2 subclasses. Furthermore, patients with high-grade HCC of the predominant Immune-high subtype had significantly better prognosis. These results provide a rationale for evaluating the immune microenvironment in addition to the usual histological/molecular classification of HCC. Conclusion: The immune microenvironment of HCC can be classified into three immunosubtypes (Immune-high, Immune-mid, and Immune-low) with additional prognostic impact on histological and molecular classification of HCC. (Hepatology 2018).

• Access to Document (DOI)

Mesenchymal–epithelial transition of pancreatic cancer cells at perineural invasion sites is induced by Schwann cells

Fujii-Nishimura Y., Yamazaki K., Masugi Y., Douguchi J., Kurebayashi Y., Kubota N., Ojima H., Kitago M., Shinoda M., Hashiguchi A., Sakamoto M.

Pathology International (Pathology International)  68 ( 4 ) 214 - 223 2018.04

ISSN  13205463

　View Summary

© 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd Epithelial–mesenchymal transition (EMT) promotes invasion and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the importance of its reverse process, mesenchymal–epithelial transition (MET), for PDAC remains unclear. We aimed to characterize the histological finding “focal differentiation” in PDAC at perineural invasion sites in the context of MET and to investigate the role of Schwann cells in inducing tumor MET. Tumor differentiation and immunohistochemical expressions of E-cadherin, SMAD3, and vimentin at perineural invasion sites were examined in 168 PDAC tissues. Four PDAC cell lines were co-cultured with Schwann cells to investigate cell morphology, motility, or EMT-related markers using immunocytochemistry and quantitative PCR. Of 168 tumors, 124 (74%) showed focal differentiation with enhanced E-cadherin membrane expression (P < 0.001) and decreased nuclear accumulation of SMAD3 (P < 0.001). Among 115 PDACs harboring grade 1/2 tumor, tumors with focal differentiation showed worse survival compared to those without focal differentiation (P = 0.019). PDAC cells co-cultured with Schwann cells demonstrated a sheet-like appearance, increased E-cadherin expression, decreased expressions of SMAD3 and vimentin, and reduced cell motility. In conclusion, MET-like change is induced by Schwann cells, suggesting that Schwann cells contribute to PDAC colonization in pancreatic nerves through activating the MET machinery inside tumor cells in the pancreatic tumor microenvironment.

• Access to Document (DOI)

Generation of allo-antigen-specific induced Treg stabilized by vitamin C treatment and its application for prevention of acute graft versus host disease model

Kasahara, Hidenori, Kondo, Taisuke, Nakatsukasa, Hiroko, Chikuma, Shunsuke, Ito, Minako, Ando, Makoto, Kurebayashi, Yutaka, Sekiya, Takashi, Yamada, Taketo, Okamoto, Shinichiro, Yoshimura, Akihiko

INTERNATIONAL IMMUNOLOGY 29 ( 10 ) 457 - 469 2017.10

Research paper (scientific journal), Joint Work,  ISSN  0953-8178

• Access to Document (DOI)

Role of PI3K/Akt and mTOR complexes in Th17 cell differentiation

Nagai, Shigenori, Kurebayashi, Yutaka, Koyasu, Shigeo

INOSITOL PHOSPHOLIPID SIGNALING IN PHYSIOLOGY AND DISEASE 1280   30 - 34 2013

Research paper (scientific journal), Joint Work,  ISSN  0077-8923

• Access to Document (DOI)

Dynamic regulation of T(h)17 differentiation by oxygen concentrations

Ikejiri, Ai, Nagai, Shigenori, Goda, Nobuhito, Kurebayashi, Yutaka, Osada-Oka, Mayuko, Takubo, Keiyo, Suda, Toshio, Koyasu, Shigeo

INTERNATIONAL IMMUNOLOGY 24 ( 3 ) 137 - 146 2012.03

Research paper (scientific journal), Joint Work,  ISSN  0953-8178

• Access to Document (DOI)