Researcher basic information

• PhD, Osaka University, Mar. 2003

• https://researchmap.jp/molonc-210401?lang=en

• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=202101019153417896
• http://www.igm.hokudai.ac.jp/neuroimmune/index.html

• 50632866

• 202101019153417896

• 細胞生物学
• 慢性炎症 サイトカイン
• 免疫学 IL-6アンプ

• Life Science, Molecular biology

Research activity information

• RNF213-TRAF2 interaction enhances inflammatory responses via NF-κB activation in moyamoya disease.
  Mitsutaka Yasuda; Kaoru Murakami; Jing-Jing Jiang; Masaki Ito; Yuki Tanaka; Hiroki Tanaka; Rie Hasebe; Takeshi Yamasaki; Ari Hashimoto; Shimpei I Kubota; Shintaro Hojyo; Tatsuya Atsumi; Shigeru Hashimoto; Masaaki Murakami; Miki Fujimura
  International immunology, 27 Mar. 2026, [International Magazine]
  English, Scientific journal, Moyamoya disease (MMD) is a cerebrovascular disorder that predominantly affects East Asian populations. It is characterized by progressive stenosis or occlusion of terminal internal carotid arteries. Although inflammatory and autoimmune responses have been implicated in MMD pathogenesis, the precise molecular mechanisms underlying the disease remain poorly understood. RNF213, a key susceptibility gene for MMD, has been linked to inflammatory signaling; however, its role in NF-κB-driven inflammation remains unclear. Here, we identify RNF213 as a critical regulator of the IL-6 amplifier (IL6-Amp), a mechanism that enhances NF-κB-mediated inflammation in the presence of IL-6-STAT3 in non-immune cells. RNF213 knockdown reduced IL-6 expression in H4 cells, a model for IL6-Amp induction via tumor necrosis factor (TNF)-α and IL-6 co-stimulation, selectively suppressing NF-κB target genes. In vivo, RNF213 depletion attenuated inflammation in an NF-κB-dependent imiquimod-induced ear swelling model. The MMD-associated RNF213 p.R4810K variant enhanced NF-κB activation by strengthening the interaction between RNF213 and TRAF2, a key adaptor in TNF-α-NF-κB signaling. Consistent with these findings, histopathological analysis of superficial temporal arteries from MMD patients revealed genotype-dependent IL6-Amp activation, with pronounced phosphorylation of NF-κB p65 and STAT3 in homozygous carriers. In contrast, heterozygous and wild-type vessels showed minimal basal activation, but in vitro stimulation of arachnoid cells from a heterozygous patient recapitulated IL6-Amp responsiveness. Collectively, these findings establish RNF213 as a pivotal regulator of NF-κB-driven inflammation and suggest that the p.R4810K variant amplifies inflammatory signaling, thereby contributing to MMD pathogenesis. This study not only advances our understanding of MMD pathophysiology but also highlights potential therapeutic strategies targeting inflammation.
• GGT1 is a SNP eQTL gene involved in STAT3 activation and associated with the development of Post-ERCP pancreatitis.
  Ryutaro Furukawa; Masaki Kuwatani; Jing-Jing Jiang; Yuki Tanaka; Rie Hasebe; Kaoru Murakami; Kumiko Tanaka; Noriyuki Hirata; Izuru Ohki; Ikuko Takahashi; Takeshi Yamasaki; Yuta Shinohara; Shunichiro Nozawa; Shintaro Hojyo; Shimpei I Kubota; Shigeru Hashimoto; Satoshi Hirano; Naoya Sakamoto; Masaaki Murakami
  Scientific reports, 14, 1, 12224, 12224, 28 May 2024, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Post-ERCP pancreatitis (PEP) is an acute pancreatitis caused by endoscopic-retrograde-cholangiopancreatography (ERCP). About 10% of patients develop PEP after ERCP. Here we show that gamma-glutamyltransferase 1 (GGT1)-SNP rs5751901 is an eQTL in pancreatic cells associated with PEP and a positive regulator of the IL-6 amplifier. More PEP patients had the GGT1 SNP rs5751901 risk allele (C) than that of non-PEP patients at Hokkaido University Hospital. Additionally, GGT1 expression and IL-6 amplifier activation were increased in PEP pancreas samples with the risk allele. A mechanistic analysis showed that IL-6-mediated STAT3 nuclear translocation and STAT3 phosphorylation were suppressed in GGT1-deficient cells. Furthermore, GGT1 directly associated with gp130, the signal-transducer of IL-6. Importantly, GGT1-deficiency suppressed inflammation development in a STAT3/NF-κB-dependent disease model. Thus, the risk allele of GGT1-SNP rs5751901 is involved in the pathogenesis of PEP via IL-6 amplifier activation. Therefore, the GGT1-STAT3 axis in pancreas may be a prognosis marker and therapeutic target for PEP.
• DDX6 is involved in the pathogenesis of inflammatory diseases via NF-κB activation
  Seiichiro Naito; Hiroki Tanaka; Jing-Jing Jiang; Masato Tarumi; Ari Hashimoto; Yuki Tanaka; Kaoru Murakami; Shimpei I. Kubota; Shintaro Hojyo; Shigeru Hashimoto; Masaaki Murakami
  Biochemical and Biophysical Research Communications, 703, 149666, 149666, Elsevier BV, Apr. 2024
  Scientific journal
• An inflammatory bowel disease-associated SNP increases local thyroglobulin expression to develop inflammation in miniature dachshunds
  Yong Bin Teoh; Jing-Jing Jiang; Takeshi Yamasaki; Noriyuki Nagata; Toshiki Sugawara; Rie Hasebe; Hiroshi Ohta; Noboru Sasaki; Nozomu Yokoyama; Kensuke Nakamura; Yumiko Kagawa; Mitsuyoshi Takiguchi; Masaaki Murakami
  Frontiers in Veterinary Science, 10, Frontiers Media SA, 14 Jul. 2023, [Peer-reviewed]
  Scientific journal, Inflammatory colorectal polyp (ICRP) in miniature dachshunds (MDs) is a chronic inflammatory bowel disease (IBD) characterized by granulomatous inflammation that consists of neutrophil infiltration and goblet cell hyperplasia in the colon. Recently, we identified five MD-associated single-nucleotide polymorphisms (SNPs), namely PLG, TCOF1, TG, COL9A2, and COL4A4, by whole-exome sequencing. Here, we investigated whether TG c.4567C>T (p.R1523W) is associated with the ICRP pathology. We found that the frequency of the T/T SNP risk allele was significantly increased in MDs with ICRP. In vitro experiments showed that TG expression in non-immune cells was increased by inducing the IL-6 amplifier with IL-6 and TNF-α. On the other hand, a deficiency of TG suppressed the IL-6 amplifier. Moreover, recombinant TG treatment enhanced the activation of the IL-6 amplifier, suggesting that TG is both a positive regulator and a target of the IL-6 amplifier. We also found that TG expression together with two NF-κB targets, IL6 and CCL2, was increased in colon samples isolated from MDs with the T/T risk allele compared to those with the C/C non-risk allele, but serum TG was not increased. Cumulatively, these results suggest that the T/T SNP is an expression quantitative trait locus (eQTL) of TG mRNA in the colon, and local TG expression triggered by this SNP increases the risk of ICRP in MDs via the IL-6 amplifier. Therefore, TG c.4567C>T is a diagnostic target for ICRP in MDs, and TG-mediated IL-6 amplifier activation in the colon is a possible therapeutic target for ICRP.
• GM-CSF Promotes the Survival of Peripheral-Derived Myeloid Cells in the Central Nervous System for Pain-Induced Relapse of Neuroinflammation.
  Shiina Matsuyama; Reiji Yamamoto; Kaoru Murakami; Nobuhiko Takahashi; Rieko Nishi; Asuka Ishii; Junko Nio-Kobayashi; Nobuya Abe; Kumiko Tanaka; Jing-Jing Jiang; Tadafumi Kawamoto; Toshihiko Iwanaga; Yuta Shinohara; Takeshi Yamasaki; Izuru Ohki; Shintaro Hojyo; Rie Hasebe; Shimpei I Kubota; Noriyuki Hirata; Daisuke Kamimura; Shigeru Hashimoto; Yuki Tanaka; Masaaki Murakami
  Journal of immunology (Baltimore, Md. : 1950), 211, 1, 34, 42, 01 Jul. 2023, [International Magazine]
  English, Scientific journal, We recently discovered a (to our knowledge) new neuroimmune interaction named the gateway reflex, in which the activation of specific neural circuits establishes immune cell gateways at specific vessel sites in organs, leading to the development of tissue-specific autoimmune diseases, including a multiple sclerosis (MS) mouse model, experimental autoimmune encephalomyelitis (EAE). We have reported that peripheral-derived myeloid cells, which are CD11b+MHC class II+ and accumulate in the fifth lumbar (L5) cord during the onset of a transfer model of EAE (tEAE), play a role in the pain-mediated relapse via the pain-gateway reflex. In this study, we investigated how these cells survive during the remission phase to cause the relapse. We show that peripheral-derived myeloid cells accumulated in the L5 cord after tEAE induction and survive more than other immune cells. These myeloid cells, which highly expressed GM-CSFRα with common β chain molecules, grew in number and expressed more Bcl-xL after GM-CSF treatment but decreased in number by blockade of the GM-CSF pathway, which suppressed pain-mediated relapse of neuroinflammation. Therefore, GM-CSF is a survival factor for these cells. Moreover, these cells were colocalized with blood endothelial cells (BECs) around the L5 cord, and BECs expressed a high level of GM-CSF. Thus, GM-CSF from BECs may have an important role in the pain-mediated tEAE relapse caused by peripheral-derived myeloid cells in the CNS. Finally, we found that blockade of the GM-CSF pathway after pain induction suppressed EAE development. Therefore, GM-CSF suppression is a possible therapeutic approach in inflammatory CNS diseases with relapse, such as MS.
• Computer model of IL-6 dependent rheumatoid arthritis in F759 mice.
  Reiji Yamamoto; Satoshi Yamada; Toru Atsumi; Kaoru Murakami; Ari Hashimoto; Seiichiro Naito; Yuki Tanaka; Izuru Ohki; Yuta Shinohara; Norimasa Iwasaki; Akihiko Yoshimura; Jing-Jing Jiang; Daisuke Kamimura; Shintaro Hojyo; Shimpei I Kubota; Shigeru Hashimoto; Masaaki Murakami
  International immunology, 35, 9, 403, 421, 25 May 2023, [International Magazine]
  English, Scientific journal, The IL-6 amplifier, which describes the simultaneous activation of STAT3 and NF-kB, in synovial fibroblasts causes the infiltration of immune cells into the joints of F759 mice. The result is a disease that resembles human rheumatoid arthritis. However, the kinetics and regulatory mechanisms of how augmented transcriptional activation by STAT3 and NF-kB leads to F759 arthritis is unknown. We here show that the STAT3-NF-κB complex is present in the cytoplasm and nucleus and accumulates around NFkB binding sites of the IL-6 promoter region and established a computer model that shows IL-6 and IL-17 signaling promotes the formation of the STAT3-NF-κB complex followed by its binding on promoter regions of NF-kB target genes to accelerate inflammatory responses, including the production of IL-6, epiregulin, and CCL2, phenotypes consistent with in vitro experiments. The binding also promoted cell growth in the synovium and the recruitment of Th17 cells and macrophages in the joints. Anti-IL-6 blocking antibody treatment inhibited inflammatory responses even at the late phase, but anti-IL-17 and anti-TNFα antibodies did not. However, anti-IL-17 antibody at the early phase showed inhibitory effects, suggesting that the IL-6 amplifier is dependent on IL-6 and IL-17 stimulation at the early phase, but only on IL-6 at the late phase. These findings demonstrate the molecular mechanism of F759 arthritis can be recapitulated in silico and identify a possible therapeutic strategy for IL-6 amplifier-dependent chronic inflammatory diseases.
• Dupuytren's contracture-associated SNPs increase SFRP4 expression in nonimmune cells including fibroblasts to enhance inflammation development.
  Hiroaki Kida; Jing-Jing Jiang; Yuichiro Matsui; Ikuko Takahashi; Rie Hasebe; Daisuke Kawamura; Takeshi Endo; Hiroki Shibayama; Makoto Kondoh; Yasuhiko Nishio; Kinya Nishida; Yoshihiro Matsuno; Tsukasa Oikawa; Shimpei Kubota; Shintaro Hojyo; Norimasa Iwasaki; Shigeru Hashimoto; Yuki Tanaka; Masaaki Murakami
  International immunology, 35, 7, 303, 312, 31 Jan. 2023, [International Magazine]
  English, Scientific journal, Dupuytren's contracture (DC) is an inflammatory fibrosis characterized by fibroproliferative disorders of the palmar aponeurosis, for which there is no effective treatment. Although several genome-wide association studies have identified risk alleles associated with DC, the functional linkage between these alleles and the pathogenesis remains elusive. We here focused on two SNPs associated with DC, rs16879765 and rs17171229, in secreted frizzled related protein 4 (SFRP4). We investigated the association of SRFP4 with the IL-6 amplifier, which amplifies the production of IL-6, growth factors, and chemokines in non-immune cells and aggravates inflammatory diseases via NF-κB enhancement. Knockdown of SFRP4 suppressed activation of the IL-6 amplifier in vitro and in vivo, whereas the overexpression of SFRP4 induced the activation of NF-κB-mediated transcription activity. Mechanistically, SFRP4 induced NF-κB activation by directly binding to molecules of the ubiquitination SFC complex, such as IkBα and βTrCP, followed by IkBα degradation. Furthermore, SFRP4 expression was significantly increased in fibroblasts derived from DC patients bearing the risk alleles. Consistently, fibroblasts with the risk alleles enhanced activation of the IL-6 amplifier. These findings indicate that the IL-6 amplifier is involved in the pathogenesis of DC, particularly in patients harboring the SFRP4 risk alleles. Therefore, SFRP4 is a potential therapeutic target for various inflammatory diseases and disorders, including DC.
• Sjögren's syndrome-associated SNPs increase GTF2I expression in salivary gland cells to enhance inflammation development.
  Shuhei Shimoyama; Ikuma Nakagawa; Jing-Jing Jiang; Isao Matsumoto; John A Chiorini; Yoshinori Hasegawa; Osamu Ohara; Rie Hasebe; Mitsutoshi Ota; Mona Uchida; Daisuke Kamimura; Shintaro Hojyo; Yuki Tanaka; Tatsuya Atsumi; Masaaki Murakami International immunology
  International immunology, Jul. 2021
• Rhodobacter azotoformans LPS (RAP99-LPS) Is a TLR4 Agonist That Inhibits Lung Metastasis and Enhances TLR3-Mediated Chemokine Expression
  Kaoru Murakami; Daisuke Kamimura; Rie Hasebe; Mona Uchida; Nobuya Abe; Reiji Yamamoto; Jing-Jing Jiang; Yasuhiro Hidaka; Yuko Nakanishi; Shuzo Fujita; Yuki Toda; Nobuhiro Toda; Hiroki Tanaka; Shizuo Akira; Yuki Tanaka; Masaaki Murakami
  Frontiers in Immunology, 12, Frontiers Media SA, 25 May 2021
  Scientific journal, The lipopolysaccharides (LPSs) of Rhodobacter are reported to be TLR4 antagonists. Accordingly, the extract of Rhodobacter azotoformans (RAP99) is used as a health supplement for humans and animals in Japan to regulate immune responses in vivo. We previously analyzed the LPS structure of RAP99 (RAP99-LPS) and found it is different from that of E. coli-LPS but similar to lipid A from Rhodobacter sphaeroides (RSLA), a known antagonist of TLR4, with both having three C14 fatty acyl groups, two C10 fatty acyl groups, and two phosphates. Here we show that RAP99-LPS has an immune stimulatory activity and acts as a TLR4 agonist. Pretreatment of RAP99-LPS suppressed E. coli-LPS-mediated weight loss, suggesting it is an antagonist against E. coli-LPS like other LPS isolated from Rhodobacter. However, injections of RAP99-LPS caused splenomegaly and increased immune cell numbers in C57BL/6 mice but not in C3H/HeJ mice, suggesting that RAP99-LPS stimulates immune cells via TLR4. Consistently, RAP99-LPS suppressed the lung metastasis of B16F1 tumor cells and enhanced the expression of TLR3-mediated chemokines. These results suggest that RAP99-LPS is a TLR4 agonist that enhances the activation status of the immune system to promote anti-viral and anti-tumor activity in vivo.
• Increased urinary exosomal SYT17 levels in chronic active antibody-mediated rejection after kidney transplantation via the IL-6 amplifier
  Yusuke Takada; Daisuke Kamimura; Jing-Jing Jiang; Haruka Higuchi; Daiki Iwami; Kiyohiko Hotta; Yuki Tanaka; Mitsutoshi Ota; Madoka Higuchi; Saori Nishio; Tatsuya Atsumi; Nobuo Shinohara; Yoshihiro Matsuno; Takahiro Tsuji; Tatsu Tanabe; Hajime Sasaki; Naoya Iwahara; Masaaki Murakami
  International Immunology, 32, 10, 653, 662, Oxford University Press (OUP), 30 Sep. 2020
  Scientific journal, Abstract
  
  Chronic active antibody-mediated rejection (CAAMR) is a particular problem in kidney transplantation (KTx), and ~25% of grafts are lost by CAAMR. Further, the pathogenesis remains unclear, and there is no effective cure or marker. We previously found that a hyper NFκB-activating mechanism in non-immune cells, called the IL-6 amplifier, is induced by the co-activation of NFκB and STAT3, and that this activation can develop various chronic inflammatory diseases. Here, we show that synaptotagmin-17 (SYT17) is increased in an exosomal fraction of the urine from CAAMR patients, and that this increase is associated with activation of the IL-6 amplifier. Immunohistochemistry showed that SYT17 protein expression was increased in renal tubule cells of the CAAMR group. While SYT17 protein was not detectable in whole-urine samples by western blotting, urinary exosomal SYT17 levels were significantly elevated in the CAAMR group compared to three other histology groups (normal, interstitial fibrosis and tubular atrophy, and calcineurin inhibitors toxicity) after KTx. On the other hand, current clinical laboratory data could not differentiate the CAAMR group from these groups. These data suggest that urinary exosomal SYT17 is a potential diagnostic marker for CAAMR.
• Corrigendum: Orosomucoid 1 is involved in the development of chronic allograft rejection after kidney transplantation
  Haruka Higuchi; Daisuke Kamimura; Jing-Jing Jiang; Toru Atsumi; Daiki Iwami; Kiyohiko Hotta; Hiroshi Harada; Yusuke Takada; Hiromi Kanno-Okada; Kanako C Hatanaka; Yuki Tanaka; Nobuo Shinohara; Masaaki Murakami
  International Immunology, 32, 7, 493, 493, Oxford University Press (OUP), 26 Jun. 2020
  Scientific journal
• Role of Chondrocytes in the Development of Rheumatoid Arthritis Via Transmembrane Protein 147–Mediated NF ‐κB Activation
  Mitsutoshi Ota; Yuki Tanaka; Ikuma Nakagawa; Jing‐Jing Jiang; Yasunobu Arima; Daisuke Kamimura; Tomohiro Onodera; Norimasa Iwasaki; Masaaki Murakami
  Arthritis & Rheumatology, 72, 6, 931, 942, Wiley, Jun. 2020
  Scientific journal
• NEDD4 Is Involved in Inflammation Development during Keloid Formation
  Munezumi Fujita; Yuhei Yamamoto; Jing-Jing Jiang; Toru Atsumi; Yuki Tanaka; Takuto Ohki; Naoki Murao; Emi Funayama; Toshihiko Hayashi; Masayuki Osawa; Taku Maeda; Daisuke Kamimura; Masaaki Murakami
  Journal of Investigative Dermatology, 139, 2, 333, 341, Elsevier BV, Feb. 2019
  Scientific journal
• Bmi1 Regulates IκBα Degradation via Association with the SCF Complex
  Yuko Okuyama; Yuki Tanaka; Jing-Jing Jiang; Daisuke Kamimura; Akihiro Nakamura; Mitsutoshi Ota; Takuto Ohki; Daisuke Higo; Hideki Ogura; Naoto Ishii; Toru Atsumi; Masaaki Murakami
  The Journal of Immunology, 201, 8, 2264, 2272, The American Association of Immunologists, 15 Oct. 2018
  Scientific journal
• Presenilin 1 Regulates NF-κB Activation via Association with Breakpoint Cluster Region and Casein Kinase II
  Yuki Tanaka; Lavannya Sabharwal; Mitsutoshi Ota; Ikuma Nakagawa; Jing-Jing Jiang; Yasunobu Arima; Hideki Ogura; Masayasu Okochi; Masaru Ishii; Daisuke Kamimura; Masaaki Murakami
  The Journal of Immunology, 201, 8, 2256, 2263, The American Association of Immunologists, 15 Oct. 2018
  Scientific journal
• Rbm10 regulates inflammation development via alternative splicing of Dnmt3b
  Toru Atsumi; Hironao Suzuki; Jing-Jing Jiang; Yuko Okuyama; Ikuma Nakagawa; Mitsutoshi Ota; Yuki Tanaka; Takuto Ohki; Kokichi Katsunuma; Koichi Nakajima; Yoshinori Hasegawa; Osamu Ohara; Hideki Ogura; Yasunobu Arima; Daisuke Kamimura; Masaaki Murakami
  International Immunology, 29, 12, 581, 591, Oxford University Press (OUP), 31 Dec. 2017
  Scientific journal, Abstract
  
  RNA-binding motif 10 (Rbm10) is an RNA-binding protein that regulates alternative splicing, but its role in inflammation is not well defined. Here, we show that Rbm10 controls appropriate splicing of DNA (cytosine-5)-methyltransferase 3b (Dnmt3b), a DNA methyltransferase, to regulate the activity of NF-κB-responsive promoters and consequently inflammation development. Rbm10 deficiency suppressed NF-κB-mediated responses in vivo and in vitro. Mechanistic analysis showed that Rbm10 deficiency decreased promoter recruitment of NF-κB, with increased DNA methylation of the promoter regions in NF-κB-responsive genes. Consistently, Rbm10 deficiency increased the expression level of Dnmt3b2, which has enzyme activity, while it decreased the splicing isoform Dnmt3b3, which does not. These two isoforms associated with NF-κB efficiently, and overexpression of enzymatically active Dnmt3b2 suppressed the expression of NF-κB targets, indicating that Rbm10-mediated Dnmt3b2 regulation is important for the induction of NF-κB-mediated transcription. Therefore, Rbm10-dependent Dnmt3b regulation is a possible therapeutic target for various inflammatory diseases.
• Correction: Breakpoint Cluster Region–Mediated Inflammation Is Dependent on Casein Kinase II
  Jie Meng; Jing-Jing Jiang; Toru Atsumi; Hidenori Bando; Yuko Okuyama; Lavannya Sabharwal; Ikuma Nakagawa; Haruka Higuchi; Mitsutoshi Ota; Momoko Okawara; Ryuichiro Ishitani; Osamu Nureki; Daisuke Higo; Yasunobu Arima; Hideki Ogura; Daisuke Kamimura; Masaaki Murakami
  The Journal of Immunology, 198, 2, 971, 971, The American Association of Immunologists, 15 Jan. 2017
  Scientific journal
• Breakpoint Cluster Region–Mediated Inflammation Is Dependent on Casein Kinase II
  Jie Meng; Jing-Jing Jiang; Toru Atsumi; Hidenori Bando; Yuko Okuyama; Lavannya Sabharwal; Ikuma Nakagawa; Haruka Higuchi; Mitsutoshi Ota; Momoko Okawara; Ryuichiro Ishitani; Osamu Nureki; Daisuke Higo; Yasunobu Arima; Hideki Ogura; Daisuke Kamimura; Masaaki Murakami
  The Journal of Immunology, 197, 8, 3111, 3119, The American Association of Immunologists, 15 Oct. 2016
  Scientific journal
• Strong TCR-mediated signals suppress integrated stress responses induced by KDELR1 deficiency in naive T cells
  Daisuke Kamimura; Yasunobu Arima; Mineko Tsuruoka; Jing-jing Jiang; Hidenori Bando; Jie Meng; Lavannya Sabharwal; Andrea Stofkova; Naoki Nishikawa; Kotaro Higuchi; Hideki Ogura; Toru Atsumi; Masaaki Murakami
  International Immunology, 28, 3, 117, 126, Oxford University Press (OUP), 01 Mar. 2016
  Scientific journal, Abstract
  
  KDEL receptor 1 (KDELR1) regulates integrated stress responses (ISR) to promote naive T-cell survival in vivo . In a mouse line having nonfunctional KDELR1, T-Red (naive T-cell reduced) mice, polyclonal naive T cells show excessive ISR and eventually undergo apoptosis. However, breeding T-Red mice with TCR-transgenic mice bearing relatively high TCR affinity rescued the T-Red phenotype, implying a link between ISR-induced apoptosis and TCR-mediated signaling. Here, we showed that strong TCR stimulation reduces ISR in naive T cells. In mice lacking functional KDELR1, surviving naive T cells expressed significantly higher levels of CD5, a surrogate marker of TCR self-reactivity. In addition, higher TCR affinity/avidity was confirmed using a tetramer dissociation assay on the surviving naive T cells, suggesting that among the naive T-cell repertoire, those that receive relatively stronger TCR-mediated signals via self-antigens survive enhanced ISR. Consistent with this observation, weak TCR stimulation with altered peptide ligands decreased the survival and proliferation of naive T cells, whereas stimulation with ligands having higher affinity had no such effect. These results suggest a novel role of TCR-mediated signals in the attenuation of ISR in vivo .
• Role of Cytokine-Mediated Crosstalk between T Cells and Nonimmune Cells in the Pathophysiology of Multiple Sclerosis
  Daisuke Kamimura; Yasunobu Arima; Toru Atsumi; Jie Meng; Lavannya Sabharwal; Hidenori Bando; Hideki Ogura; Jing-Jing Jiang; Eric S. Huseby; Masaaki Murakami
  Multiple Sclerosis, 101, 125, Elsevier, 2016
  In book
• Naïve T Cell Homeostasis Regulated by Stress Responses and TCR Signaling
  Daisuke Kamimura; Toru Atsumi; Andrea Stofkova; Naoki Nishikawa; Takuto Ohki; Hironao Suzuki; Kokichi Katsunuma; Jing-jing Jiang; Hidenori Bando; Jie Meng; Lavannya Sabharwal; Hideki Ogura; Toshio Hirano; Yasunobu Arima; Masaaki Murakami
  Frontiers in Immunology, 6, Frontiers Media SA, 17 Dec. 2015
  Scientific journal
• KDELR1はナイーブT細胞において統合ストレス応答を調節する
  上村 大輔; 勝沼 功吉; 有馬 康伸; 熱海 徹; Jiang Jing-Jing; 板東 秀典; Meng Jie; Sabharwal Lavannya; Stofkova Andrea; 西川 直樹; 鈴木 宏尚; 小椋 英樹; 植田 尚子; 鶴岡 峰子; 原田 誠也; 小林 純也; 長谷川 孝徳; 吉田 尚弘; 古関 明彦; 三浦 郁生; 若菜 茂晴; 西田 圭吾; 北村 秀光; 深田 俊幸; 平野 俊夫; 村上 正晃
  日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, 88回・38回, [1LBA045], [1LBA045], (公社)日本生化学会, Dec. 2015
  English
• KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR
  Daisuke Kamimura; Kokichi Katsunuma; Yasunobu Arima; Toru Atsumi; Jing-jing Jiang; Hidenori Bando; Jie Meng; Lavannya Sabharwal; Andrea Stofkova; Naoki Nishikawa; Hironao Suzuki; Hideki Ogura; Naoko Ueda; Mineko Tsuruoka; Masaya Harada; Junya Kobayashi; Takanori Hasegawa; Hisahiro Yoshida; Haruhiko Koseki; Ikuo Miura; Shigeharu Wakana; Keigo Nishida; Hidemitsu Kitamura; Toshiyuki Fukada; Toshio Hirano; Masaaki Murakami
  Nature Communications, 6, 1, Springer Science and Business Media LLC, Nov. 2015
  Scientific journal
• Temporal Expression of Growth Factors Triggered by Epiregulin Regulates Inflammation Development
  Masaya Harada; Daisuke Kamimura; Yasunobu Arima; Hitoshi Kohsaka; Yuji Nakatsuji; Makoto Nishida; Toru Atsumi; Jie Meng; Hidenori Bando; Rajeev Singh; Lavannya Sabharwal; Jing-Jing Jiang; Noriko Kumai; Nobuyuki Miyasaka; Saburo Sakoda; Keiko Yamauchi-Takihara; Hideki Ogura; Toshio Hirano; Masaaki Murakami
  The Journal of Immunology, 194, 3, 1039, 1046, The American Association of Immunologists, 01 Feb. 2015
  Scientific journal
• The Gateway Reflex, which is mediated by the inflammation amplifier, directs pathogenic immune cells into the CNS
  L. Sabharwal; D. Kamimura; J. Meng; H. Bando; H. Ogura; C. Nakayama; J.-J. Jiang; N. Kumai; H. Suzuki; T. Atsumi; Y. Arima; M. Murakami
  Journal of Biochemistry, 156, 6, 299, 304, Oxford University Press (OUP), 01 Dec. 2014
  Scientific journal
• The Reverse-Direction Method Links Mass Experimental Data to Human Diseases
  Hideki Ogura; Toru Atsumi; Hidenori Bando; Lavannya Sabharwal; Moe Yamada; Jing-Jing Jiang; Akihiro Nakamura; Yasunobu Arima; Daisuke Kamimura; Masaaki Murakami
  Archivum Immunologiae et Therapiae Experimentalis, 62, 1, 41, 45, Springer Science and Business Media LLC, Feb. 2014
  Scientific journal
• Inflammation Amplifier, a New Paradigm in Cancer Biology
  Toru Atsumi; Rajeev Singh; Lavannya Sabharwal; Hidenori Bando; Jie Meng; Yasunobu Arima; Moe Yamada; Masaya Harada; Jing-Jing Jiang; Daisuke Kamimura; Hideki Ogura; Toshio Hirano; Masaaki Murakami
  Cancer Research, 74, 1, 8, 14, American Association for Cancer Research (AACR), 01 Jan. 2014
  Scientific journal, Abstract
  
  Tumor-associated inflammation can induce various molecules expressed from the tumors themselves or surrounding cells to create a microenvironment that potentially promotes cancer development. Inflammation, particularly chronic inflammation, is often linked to cancer development, even though its evolutionary role should impair nonself objects including tumors. The inflammation amplifier, a hyperinducer of chemokines in nonimmune cells, is the principal machinery for inflammation and is activated by the simultaneous stimulation of NF-κB and STAT3. We have redefined inflammation as local activation of the inflammation amplifier, which causes an accumulation of various immune cells followed by dysregulation of local homeostasis. Genes related to the inflammation amplifier have been genetically associated with various human inflammatory diseases. Here, we describe how cancer-associated genes, including interleukin (IL)-6, Ptgs2, ErbB1, Gas1, Serpine1, cMyc, and Vegf-α, are strongly enriched in genes related to the amplifier. The inflammation amplifier is activated by the stimulation of cytokines, such as TNF-α, IL-17, and IL-6, resulting in the subsequent expression of various target genes for chemokines and tumor-related genes like BCL2L11, CPNE7, FAS, HIF1-α, IL-1RAP, and SOD2. Thus, we conclude that inflammation does indeed associate with the development of cancer. The identified genes associated with the inflammation amplifier may thus make potential therapeutic targets of cancers. Cancer Res; 74(1); 8–14. ©2013 AACR.
• Erratum to Disease-Association Analysis of an Inflammation-Related Feedback Loop [Cell Reports 3, (2013) 946-959]
  Masaaki Murakami; Masaya Harada; Daisuke Kamimura; Hideki Ogura; Yuko Okuyama; Noriko Kumai; Azusa Okuyama; Rajeev Singh; Jing-Jing Jiang; Toru Atsumi; Sayaka Shiraya; Yuji Nakatsuji; Makoto Kinoshita; Hitoshi Kohsaka; Makoto Nishida; Saburo Sakoda; Nobuyuki Miyasaka; Keiko Yamauchi-Takihara; Toshio Hirano
  Cell Reports, 3, 5, 1754, 30 May 2013, [Peer-reviewed]
  English, Scientific journal
• Disease-Association Analysis of an Inflammation-Related Feedback Loop
  Masaaki Murakami; Masaya Harada; Daisuke Kamimura; Hideki Ogura; Yuko Okuyama; Noriko Kumai; Azusa Okuyama; Rajeev Singh; Jing-Jing Jiang; Toru Atsumi; Sayaka Shiraya; Yuji Nakatsuji; Makoto Kinoshita; Hitoshi Kohsaka; Makoto Nishida; Saburo Sakoda; Nobuyuki Miyasaka; Keiko Yamaguchi-Takihara; Toshio Hirano
  Cell Reports, 3, 3, 946, 959, Elsevier BV, Mar. 2013
  Scientific journal
• Hepatic Interleukin-7 Expression Regulates T Cell Responses
  Yukihisa Sawa; Yasunobu Arima; Hideki Ogura; Chika Kitabayashi; Jing-Jing Jiang; Toru Fukushima; Daisuke Kamimura; Toshio Hirano; Masaaki Murakami
  Immunity, 30, 3, 447, 457, Elsevier BV, Mar. 2009
  Scientific journal
• Long-term control of food intake and body weight by hydrodynamics-based delivery of plasmid DNA encoding leptin or CNTF
  Jingjing Jiang; Eiji Yamato; Jun-ichi Miyazaki
  The Journal of Gene Medicine, 5, 11, 977, 983, Wiley, Nov. 2003
  Scientific journal
• Sustained Expression of Fc-Fusion Cytokine Following In Vivo Electroporation and Mouse Strain Differences in Expression Levels
  J. Jiang
  Journal of Biochemistry, 133, 4, 423, 427, Oxford University Press (OUP), 01 Apr. 2003
  Scientific journal
• Intravenous Delivery of Naked Plasmid DNA for in Vivo Cytokine Expression
  Jingjing Jiang; Eiji Yamato; Jun-ichi Miyazaki
  Biochemical and Biophysical Research Communications, 289, 5, 1088, 1092, Elsevier BV, Dec. 2001
  Scientific journal

• Orosomucoid 1 is involved in the development of chronic allograft rejection after kidney transplantation.
  Haruka Higuchi; Daisuke Kamimura; Jing-Jing Jiang; Toru Atsumi; Daiki Iwami; Kiyohiko Hotta; Hiroshi Harada; Yusuke Takada; Hiromi Kanno-Okada; Kanako C Hatanaka; Yuki Tanaka; Nobuo Shinohara; Masaaki Murakami, International immunology, 32, 5, 335, 346, 08 May 2020, [International Magazine]
  Chronic allograft rejection is the most common cause of long-term allograft failure. One reason is that current diagnostics and therapeutics for chronic allograft rejection are very limited. We here show that enhanced NFκB signaling in kidney grafts contributes to chronic active antibody-mediated rejection (CAAMR), which is a major pathology of chronic kidney allograft rejections. Moreover, we found that urinary orosomucoid 1 (ORM1) is a candidate marker molecule and therapeutic target for CAAMR. Indeed, urinary ORM1 concentration was significantly higher in kidney transplant recipients pathologically diagnosed with CAAMR than in kidney transplant recipients with normal histology, calcineurin inhibitor toxicity, or interstitial fibrosis and tubular atrophy. Additionally, we found that kidney biopsy samples with CAAMR expressed more ORM1 and had higher NFκB and STAT3 activation in tubular cells than samples from non-CAAMR samples. Consistently, ORM1 production was induced after cytokine-mediated NFκB and STAT3 activation in primary kidney tubular cells. The loss- and gain-of-function of ORM1 suppressed and promoted NFκB activation, respectively. Finally, ORM1-enhanced NFκB-mediated inflammation development in vivo. These results suggest that an enhanced NFκB-dependent pathway following NFκB and STAT3 activation in the grafts is involved in the development of chronic allograft rejection after kidney transplantation and that ORM1 is a non-invasive candidate biomarker and possible therapeutic target for chronic kidney allograft rejection., English
• 軟骨細胞にはNF-κB arthritis inducer 1を介する炎症回路活性化機構が存在する
  太田 光俊; 田中 勇希; 蒋 菁菁; 中川 育磨; 樋口 はるか; 藤田 宗純; 有馬 康伸; 熱海 徹; 上村 大輔; 小野寺 智洋; 村上 正晃; 岩崎 倫政, 日本整形外科学会雑誌, 91, 8, S1728, S1728, Aug. 2017
  (公社)日本整形外科学会, Japanese
• A novel regulator of NF kappa B signaling enhances I kappa B alpha ubiquitination and promotes inflammatory disease development
  Y. Okuyama; T. Atsumi; J. -J Jiang; A. Nakamura; H. Ogura; J. Meng; D. Kamimura; N. Shii; T. Hirano; M. Murakami, EUROPEAN JOURNAL OF IMMUNOLOGY, 46, 410, 410, Aug. 2016
  English, Summary international conference