Toshinori Nakayama


Affiliation: Chiba University
Country: Japan


  1. Nakayama T, Hirahara K, Onodera A, Endo Y, Hosokawa H, Shinoda K, et al. Th2 Cells in Health and Disease. Annu Rev Immunol. 2017;35:53-84 pubmed publisher
    ..The concept of defined subsets of pathogenic Th cells may spur new, effective strategies for treating intractable chronic inflammatory disorders. ..
  2. Wada T, Hirahara K, Aoki A, Morimoto Y, Kiuchi M, Kumagai J, et al. An optimized protocol for the analysis of house dust mite (Dermatophagoides farinae)-induced neutrophil-dominant airway inflammation. J Immunol Methods. 2018;: pubmed publisher
    ..The pathogenic changes in the airway were dependent on both the frequency and dose of D. farinae exposure. Our study provides novel procedures and insight into the pathogenesis of D. farinae-induced airway inflammation in vivo. ..
  3. Yamamoto T, Endo Y, Onodera A, Hirahara K, Asou H, Nakajima T, et al. DUSP10 constrains innate IL-33-mediated cytokine production in ST2hi memory-type pathogenic Th2 cells. Nat Commun. 2018;9:4231 pubmed publisher
    ..Our data thus suggest that DUSP10 restricts IL-33-induced cytokine production in ST2hi pathogenic Th2 cells by controlling p38-GATA3 activity. ..
  4. Obata Ninomiya K, Ishiwata K, Nakano H, Endo Y, Ichikawa T, Onodera A, et al. CXCR6+ST2+ memory T helper 2 cells induced the expression of major basic protein in eosinophils to reduce the fecundity of helminth. Proc Natl Acad Sci U S A. 2018;115:E9849-E9858 pubmed publisher
    ..Taken together, these findings show that we identified a mechanism against helminth elicited by a subpopulation of IL-5-producing mTh2 cells through the accumulation of eosinophils strongly expressing MBP in the lungs. ..
  5. Hosokawa H, Kato M, Tohyama H, Tamaki Y, Endo Y, Kimura M, et al. Methylation of Gata3 protein at Arg-261 regulates transactivation of the Il5 gene in T helper 2 cells. J Biol Chem. 2015;290:13095-103 pubmed publisher
    ..Thus, arginine methylation appears to play a pivotal role in the organization of Gata3 complexes and the target gene specificity of Gata3. ..
  6. Endo Y, Hirahara K, Iinuma T, Shinoda K, Tumes D, Asou H, et al. The interleukin-33-p38 kinase axis confers memory T helper 2 cell pathogenicity in the airway. Immunity. 2015;42:294-308 pubmed publisher
    ..Thus, IL-33-ST2-p38 signaling appears to directly instruct pathogenic memory Th2 cells to produce IL-5 and induce eosinophilic inflammation. ..
  7. Onodera A, Nakayama T. Epigenetics of T cells regulated by Polycomb/Trithorax molecules. Trends Mol Med. 2015;21:330-40 pubmed publisher
    ..In this review, we focus on Polycomb and Trithorax proteins, well-characterized epigenetic modulators, and discuss their role in the epigenetic regulation of T cell differentiation and function. ..
  8. Morimoto Y, Hirahara K, Kiuchi M, Wada T, Ichikawa T, Kanno T, et al. Amphiregulin-Producing Pathogenic Memory T Helper 2 Cells Instruct Eosinophils to Secrete Osteopontin and Facilitate Airway Fibrosis. Immunity. 2018;49:134-150.e6 pubmed publisher
    ..Thus, the IL-33-amphiregulin-osteopontin axis directs fibrotic responses in eosinophilic airway inflammation and is a potential target for the treatment of fibrosis induced by chronic allergic disorders. ..
  9. Onodera A, Tumes D, Watanabe Y, Hirahara K, Kaneda A, Sugiyama F, et al. Spatial Interplay between Polycomb and Trithorax Complexes Controls Transcriptional Activity in T Lymphocytes. Mol Cell Biol. 2015;35:3841-53 pubmed publisher
    ..Therefore, spatial cooperative gene regulation by the PcG and TrxG complexes may represent a novel mechanism regulating the transcriptional identity of differentiated cells. ..

More Information


  1. Nakayama T, Yamashita M. The TCR-mediated signaling pathways that control the direction of helper T cell differentiation. Semin Immunol. 2010;22:303-9 pubmed publisher
    ..This review focuses on the TCR signal strength and the TCR-mediated signaling pathways that control the differentiation into these four Th cell subsets. ..
  2. Shinoda K, Hirahara K, Iinuma T, Ichikawa T, Suzuki A, Sugaya K, et al. Thy1+IL-7+ lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation. Proc Natl Acad Sci U S A. 2016;113:E2842-51 pubmed publisher
    ..Thus, Thy1(+)IL-7-producing LECs control chronic allergic airway inflammation by providing a survival niche for memory-type Tpath2 cells. ..
  3. Hirahara K, Nakayama T. CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm. Int Immunol. 2016;28:163-71 pubmed publisher
    ..To this end, we propose another model--the pathogenic T-helper population disease-induction model--as a possible mechanism for the induction and/or persistence of immune-mediated inflammatory diseases. ..
  4. Endo Y, Asou H, Matsugae N, Hirahara K, Shinoda K, Tumes D, et al. Obesity Drives Th17 Cell Differentiation by Inducing the Lipid Metabolic Kinase, ACC1. Cell Rep. 2015;12:1042-55 pubmed publisher
    ..Thus, ACC1 confers the appropriate function of RORγt through fatty acid synthesis and regulates the obesity-related pathology of Th17 cells. ..
  5. Watanabe Y, Onodera A, Kanai U, Ichikawa T, Obata Ninomiya K, Wada T, et al. Trithorax complex component Menin controls differentiation and maintenance of T helper 17 cells. Proc Natl Acad Sci U S A. 2014;111:12829-34 pubmed publisher
    ..Thus, Menin orchestrates Th17 cell differentiation and function by regulating both the induction and maintenance of target gene expression. ..
  6. Endo Y, Yokote K, Nakayama T. The obesity-related pathology and Th17 cells. Cell Mol Life Sci. 2017;74:1231-1245 pubmed publisher
  7. Shinoda K, Hirahara K, Nakayama T. Maintenance of pathogenic Th2 cells in allergic disorders. Allergol Int. 2017;66:369-376 pubmed publisher
    ..A greater understanding of the functional molecules or signaling pathways that regulate the inflammatory niche for Tpath2 cells may aid in the design of more effective treatments for chronic inflammatory disorders. ..
  8. Onodera A, Kiuchi M, Kokubo K, Kato M, Ogino T, Horiuchi S, et al. Menin Controls the Memory Th2 Cell Function by Maintaining the Epigenetic Integrity of Th2 Cells. J Immunol. 2017;199:1153-1162 pubmed publisher
    ..This study confirmed the critical role of Menin in Th2 cell-mediated immune responses. ..
  9. Mato N, Hirahara K, Ichikawa T, Kumagai J, Nakayama M, Yamasawa H, et al. Memory-type ST2+CD4+ T cells participate in the steroid-resistant pathology of eosinophilic pneumonia. Sci Rep. 2017;7:6805 pubmed publisher
  10. Hayashizaki K, Kimura M, Tokoyoda K, Hosokawa H, Shinoda K, Hirahara K, et al. Myosin light chains 9 and 12 are functional ligands for CD69 that regulate airway inflammation. Sci Immunol. 2016;1:eaaf9154 pubmed publisher
    ..Thus, CD69-Myl9/12 interaction is a key event in the recruitment of activated CD69+ T cells to inflamed tissues and could be a therapeutic target for intractable airway inflammatory diseases. ..
  11. request reprint
    Nakayama T, Kimura M. Memory Th1/Th2 cell generation controlled by Schnurri-2. Adv Exp Med Biol. 2010;684:1-10 pubmed
    ..A repressor molecule Shn-2 plays an important role in this process. ..
  12. Nakayama T, Yamashita M. Critical role of the Polycomb and Trithorax complexes in the maintenance of CD4 T cell memory. Semin Immunol. 2009;21:78-83 pubmed publisher
    ..Therefore, in memory CD4 T cells, PcG and TrxG genes appear to control distinct processes in a distinct manner, which indicates a novel regulatory feature of the PcG/TrxG genes. ..