Faculty Profiles - MAEDA Yoshinobu

MISC - MAEDA Yoshinobu

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Dynamic Shifts in Inflammation and Fibrotic Remodeling in Post-HSCT Bronchiolitis Obliterans: A Spatial Transcriptomics Study

Akira Yamamoto, Nobuharu Fujii, Keisuke Seike, Seiichiro Sugimoto, Yusuke Naoi, Yui Kambara, Kanako Fujiwara, Toshiki Terao, Tadashi Oyama, Mari Kunihiro, Takumi Kondo, Hiroki Kobayashi, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Shinichi Toyooka, Yoshinobu Maeda

Blood 2024.11

Language：English

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<jats:p>Bronchiolitis obliterans (BO) is a severe complication following hematopoietic stem cell transplantation (HSCT), significantly impacting patients' prognosis and quality of life. Despite its clinical importance, the underlying pathophysiological mechanisms remain poorly understood.</jats:p>
<jats:p>We analyzed lung specimens from three patients who developed BO post-HSCT and subsequently underwent lung transplantation. All patients had acute lymphoblastic leukemia as their primary disease and developed BO 1-2 years after HSCT. Healthy lung regions from two cancer patients served as controls. Using NanoString GeoMx Digital Spatial Profiling, we performed transcriptional profiling with the Human Whole Transcriptome Atlas on 94 regions of interest (ROIs). BO lesions were classified based on our previously established staging system (Kuroi T et al. Int J Hematol. 2021) and analyzed for both inner and outer bronchiolar regions.</jats:p>
<jats:p>Linear mixed model analysis identified significant differential gene expression between BO and control groups. GO enrichment analysis highlighted biological processes such as phagocytosis, positive regulation of leukocyte activation, and cell activation, indicating a close association with immune cells, particularly macrophages, which are known to obstruct bronchioles in BO. Processes such as regulation of cell-cell adhesion and post-Golgi vesicle-mediated transport were also enriched, suggesting involvement in extracellular matrix remodeling and fibroblast activation. GSEA further identified significant processes, including inflammatory response, defense response, positive regulation of response to stimulus, and vesicle-mediated transport. These results suggest an interplay between immune response and tissue remodeling. Notably, changes in the expression of genes such as HES1, IGF2BP2, PTPRF, and ITGB2, which are involved in cell adhesion and cytoskeletal reorganization, were closely associated with fibroblast activation and macrophage infiltration. These findings parallel the fibrosis process observed in BO following lung transplantation, where macrophage infiltration and myofibroblast activation are critical. Given these insights, our focus shifted to the dynamics of macrophages and myofibroblasts, aiming to understand their roles in the progression from inflammation to tissue remodeling.</jats:p>
<jats:p>CD68, a pan-macrophage marker, showed higher expression in Early and Middle-outside stages (Inflammatory Phase) of BO, but significantly decreased in Middle-inside and Late stages (Remodeling Phase) as the disease progressed. Unsupervised clustering analysis revealed distinct gene expression profiles between these phases, suggesting a temporal shift in disease mechanisms as BO progresses from inner bronchioles outwards. Correlation analysis revealed significant associations between CD68 and JAK1/STAT1 expression, as well as genes associated with myofibroblast activity and extracellular matrix remodeling (e.g., ACTA2, TGFB1). These findings suggest a coordinated process of inflammation and remodeling in BO, potentially involving the JAK-STAT pathway.</jats:p>
<jats:p>Linear mixed model analysis revealed distinct gene expression patterns between Inflammatory and Remodeling Phases, characterized by inflammatory/proliferation-related genes (e.g., CXCL6, HLA-family) and tissue remodeling/protein synthesis and genes (e.g., ITGB1, RPL and RPS families), respectively. This transition aligns with changes in macrophage-related gene expression. Pathway analysis revealed enrichment of translation, ribosomal activity, and metabolic processes in the Remodeling Phase, indicating a dynamic shift in biological activities as BO progresses.</jats:p>
<jats:p>In conclusion, this study reveals a transition in BO pathology from inflammation to remodeling, with macrophages playing a central role. The coordinated changes in gene expression provide a comprehensive picture of BO progression. These insights into post-HSCT BO pathophysiology highlight potential therapeutic targets in macrophage function and tissue remodeling pathways, suggesting possibilities for stage-specific interventions in BO treatment.</jats:p>
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DOI： 10.1182/blood-2024-202251

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The Role of Salt and Microbiota in the Pathophysiology of GVHD

藤原英晃, 前田嘉信, 西森久和

ソルト・サイエンス研究財団助成研究報告集 2 医学食品科学編 2022 2024

ABC-DLBCLにおけるCD79B発現低下の臨床的・生物学的意義の解明と検証

直井友亮, 直井友亮, 千々松良太, 浦田知宏, 角南一貴, 今井利, 名和由一郎, 平松靖史, 山本和彦, 藤井総一郎, 吉田功, 矢野朋文, 高田尚良, 佐藤康晴, 前田嘉信, 遠西大輔

日本リンパ網内系学会会誌 64 2024

CD79 Expression Is Associated with Cell-of-Origin and Outcome in Diffuse Large B-Cell Lymphoma

Yusuke Naoi, Ryota Chijimatsu, Tomohiro Urata, Kazutaka Sunami, Toshi Imai, Yuichiro Nawa, Yasushi Hiramatsu, Kazuhiko Yamamoto, Soichiro Fujii, Isao Yoshida, Tomofumi Yano, Kazuhiro Ikeuchi, Hiroki Kobayashi, Katsuma Tani, Hiroyuki Murakami, Hideki Ujiie, Yasuharu Sato, Katsuyoshi Takata, Merrill Boyle, Aixiang Jiang, Yoshinobu Maeda, David W. Scott, Daisuke Ennishi

BLOOD 142 2023.11

増悪と抑制を司るアレルギーメディエーターダニ抗原による気道過敏性誘発マウスモデルにおけるインターロイキン-22 binding proteinの役割の検討

角南良太, 肥後寿夫, 尾関太一, 中村尚季, 妹尾賢, 谷口暁彦, 前田嘉信, 宮原信明

アレルギー 72 ( 6-7 ) 909 - 909 2023.8

間質性肺炎急性増悪に対する免疫グロブリン静注療法の効果

市川裕久, 肥後寿夫, 中村尚季, 藤井昌学, 松岡克浩, 関祥子, 和田学政, 須崎規之, 永田拓也, 荒川裕佳子, 宮原信明, 森由弘, 丸川雅臣, 前田嘉信, 木浦勝行

日本呼吸器学会誌 12 ( 増刊 ) 289 - 289 2023.3

重症喘息患者の増悪予測因子に関する前向き観察研究(Okayama-SARP)

肥後寿夫, 後川真輝, 谷口暁彦, 板野純子, 小田尚廣, 塩田雄太郎, 荒川裕佳子, 森由弘, 國近尚美, 高田一郎, 洲脇俊充, 中西徳彦, 谷本安, 前田嘉信, 木浦勝行, 宮原信明

日本呼吸器学会誌 12 ( 増刊 ) 315 - 315 2023.3

臍帯血移植後にHTLV-1感染T細胞の多クローン性増殖を伴って発症した肺合併症に対しCCR4抗体が著効した一例

松原千哲, 松岡賢市, 近藤歌穂, 藤原加奈子, 寺尾俊紀, 植田裕子, 松村彰文, 守山喬史, 村上裕之, 近藤匠, 清家圭介, 藤原英晃, 淺田騰, 遠西大輔, 西森久和, 藤井敬子, 藤井伸治, 中島誠, 中島誠, 内丸薫, 前田嘉信

日本血液学会学術集会抄録(Web) 85th 2023

DLBCLにおけるCD79発現の生物学的意義と臨床的重要性の解明

直井友亮, 千々松良太, 浦田和宏, 角南一貴, 今井利, 名和由一郎, 平松靖史, 山本和彦, 藤井総一郎, 吉田功, 矢野朋文, 池内一廣, 小林宏紀, 谷勝真, 村上裕之, 氏家英貴, 佐藤康晴, Boyle Merrill, Jiang Aixiang, 前田嘉信, Scott David W., 遠西大輔

日本血液学会学術集会 84回 915 - 915 2022.10

DLBCLにおけるCD79発現の生物学的意義と臨床的重要性の解明

日本血液学会学術集会 84回 915 - 915 2022.10

慢性好酸球性肺炎合併重症喘息に対してBenralizumabを投与した症例

妹尾賢, 谷口暁彦, 藤井昌学, 中村尚季, 角南良太, 肥後寿夫, 前田嘉信, 木浦勝行, 宮原信明

日本呼吸器学会誌 11 ( 増刊 ) 295 - 295 2022.4

Influence of oral microbiota on graft-versus-host disease and its role as a therapeutic target

神原由依, 藤原英晃, 山本晃, 國廣まり, 大山矩史, 近藤匠, 淺田騰, 遠西大輔, 西森久和, 藤井伸治, 藤井敬子, 松岡賢市, 前田嘉信, 前田嘉信

日本造血・免疫細胞療法学会総会プログラム・抄録集 45th 2022

Analysis of cryopreserved unrelated donor bone marrow transplantation under the COVID-19 pandemic

松村彰文, 藤原英晃, 植田裕子, 守山喬史, 村上裕之, 住井優一, 浦田知宏, 木村真衣子, 近藤匠, 浅田騰, 遠西大輔, 西森久和, 松岡賢市, 藤井敬子, 藤井伸治, 鴨井千尋, 前田嘉信

日本造血・免疫細胞療法学会総会プログラム・抄録集 44th 2022

Modification of post-transplant cyclophosphamide and tacrolimus in haploidentical transplantation

寺尾俊紀, 松岡賢市, 近藤匠, 高須賀裕樹, 鴨井千尋, 植田裕子, 松村彰文, 松原千哲, 近藤歌穂, 藤原英晃, 淺田騰, 遠西大輔, 西森久和, 藤井敬子, 藤井伸治, 前田嘉信

日本造血・免疫細胞療法学会総会プログラム・抄録集 45th 2022

Open-label, randomized study to calcium drink for prevention of citrate toxicity of PBSC donor

藤井敬子, 藤井敬子, 藤井伸治, 藤井伸治, 三橋利晴, 住居優一, 住居優一, 谷勝真, 谷勝真, 浦田知宏, 浦田知宏, 木村真衣子, 木村真衣子, 近藤匠, 藤原英晃, 淺田騰, 遠西大輔, 西森久和, 松岡賢市, 大塚文男, 前田嘉信

日本造血・免疫細胞療法学会総会プログラム・抄録集 45th 2022

Gilteritinib maintenance therapy post-SCT improves the prognosis of patients with R/R FLT3mut AML

寺尾俊紀, 松岡賢市, 植田裕子, 松村彰文, 松原千哲, 近藤歌穂, 近藤匠, 藤原英晃, 淺田騰, 遠西大輔, 西森久和, 藤井敬子, 藤井伸治, 前田嘉信

日本造血・免疫細胞療法学会総会プログラム・抄録集 45th 2022

Impact of previous thoracic radiation therapy on the efficacy of immune checkpoint inhibitors in advanced non-small-cell lung cancer (vol 51, pg 279, 2021) International journal

Shinobu Hosokawa, Eiki Ichihara, Akihiro Bessho, Daijiro Harada, Koji Inoue, Takuo Shibayama, Daizo Kishino, Shingo Harita, Nobuaki Ochi, Naohiro Oda, Naofumi Hara, Katsuyuki Hotta, Yoshinobu Maeda, Katsuyuki Kiura

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 51 ( 8 ) 1348 - 1348 2021.8

Impact on second-line treatment after failure of immune checkpoint inhibitor (ICI) combination chemotherapy in extensive-disease small cell lung cancer: Experience of the Okayama Lung Cancer Study Group.

Yuka Kato, Taku Noumi, Kazuhiko Saeki, Kiichiro Ninomiya, Toshio Kubo, Masanori Fujii, Kammei Rai, Eiki Ichihara, Kadoaki Ohashi, Masahiro Tabata, Katsuyuki Hotta, Toshiyuki Kozuki, Yoshinobu Maeda, Katsuyuki Kiura

JOURNAL OF CLINICAL ONCOLOGY 39 ( 15 ) 2021.5

移植後シクロホスファミドを用いた血縁者間HLA半合致移植後に最重症遅発性肝類洞閉塞症候群を合併した非定型慢性骨髄性白血病

北村亘, 藤井伸治, 藤井伸治, 大西秀樹, 高須賀裕樹, 大山矩史, 村上裕之, 木村真衣子, 近藤匠, 松田真幸, 池川俊太郎, 池川俊太郎, 藤原英晃, 淺田騰, 遠西大輔, 遠西大輔, 西森久和, 藤井敬子, 藤井敬子, 松岡賢市, 木口亨, 柳井広之, 吉野正, 前田嘉信

臨床血液 62 ( 6 ) 654 - 655 2021

EBV viremia with NK/T cells as well as B cells after hematopoietic stem cell transplantation

大山矩史, 西森久和, 村上裕之, 高須賀裕樹, 北村亘, 藤原英晃, 淺田騰, 藤井敬子, 藤井伸治, 遠西大輔, 松岡賢市, 前田嘉信

日本血液学会学術集会抄録(Web) 83rd 2021

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MISC - MAEDA Yoshinobu