Okazaki Lab | Publications

1. Sugiura D, Maruhashi T, Okazaki IM, Shimizu K, Maeda TK, Takemoto T, and Okazaki T.
Restriction of PD-1 function by cis-PD-L1/CD80 interactions is required for optimal T cell responses.
Science, First Release (Apr 18, 2019)

2. Mizuno R, Sugiura D, Shimizu K, Maruhashi T, Watada M, Okazaki IM, and Okazaki T.
PD-1 primarily targets TCR signal in the inhibition of functional T cell activation.
Frontiers in Immunology, 10: 630, 2019

3. Maeda TK, Sugiura D, Okazaki IM, Maruhashi T, and Okazaki T.
Atypical motifs in the cytoplasmic region of the inhibitory immune co-receptor LAG-3 inhibit T cell activation.
Journal of Biological Chemistry, 294(15): 6017-6026, 2019

4. Mizuno R, Maruhashi T, Sugiura D, Shimizu K, Watada M, Okazaki IM, and Okazaki T.
PD-1 efficiently inhibits T cell activation even in the presence of co-stimulation through CD27 and GITR.
Biochemical and Biophysical Research Communications, 511(3): 491-497, 2019

5. Maruhashi T, Okazaki IM, Sugiura D, Takahashi S, Maeda TK, Shimizu K, and Okazaki T.
LAG-3 inhibits the activation of CD4+ T cells that recognize stable pMHCII through its conformation-dependent recognition of pMHCII.
Nature Immunology, 19(12): 1415-1426, 2018

6. Nishijima H, Kajimoto T, Matsuoka Y, Mouri Y, Morimoto J, Matsumoto M, Kawano H, Nishioka Y, Uehara H, Izumi K, Tsuneyama K, Okazaki IM, Okazaki T, Hosomichi K, Shiraki A, Shibutani M, Mitsumori K, and Matsumoto M.
Paradoxical development of polymyositis-like autoimmunity through augmented expression of autoimmune regulator (AIRE).
Journal of Autoimmunity, 86: 75-92, 2018

7. Hayakawa Y, Kawada M, Nishikawa H, Ochiya T, Saya H, Seimiya H, Yao R, Hayashi M, Kai C, Matsuda A, Naoe T, Ohtsu A, Okazaki T, Saji H, Sata M, Sugimura H, Sugiyama Y, Toi M, and Irimura T.
Report on the use of non-clinical studies in the regulatory evaluation of oncology drugs.
Cancer Science, 107(2): 189-202, 2016

8. Okazaki T, Chikuma S, Iwai Y, Fagarasan S, and Honjo T.
A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application.
Nature Immunology, 14(12): 1212-1218, 2013

9. Iwamoto S, Kido M, Aoki N, Nishiura H, Maruoka R, Ikeda A, Okazaki T, Chiba T, and Watanabe N.
TNF-α is essential in the induction of fatal autoimmune hepatitis in mice through upregulation of hepatic CCL20 expression.
Clinical Immunology, 146(1): 15-25, 2013

10. Sugino Y, Nishikawa N, Yoshimura K, Kuno S, Hayashi Y, Yoshimura N, Okazaki T, Kanematsu A, and Ogawa O.
BALB/c-Fcgr2bPdcd1 mouse expressing anti-urothelial antibody is a novel model of autoimmune cystitis.
Scientific Reports, 2: 317, 2012

11. Jin HT, Ahmed R, and Okazaki T.
Role of PD-1 in Regulating T-Cell Immunity.
Current Topics in Microbiology and Immunology, 350:17-37, 2011

12. Iwamoto S, Kido M, Aoki N, Nishiura H, Maruoka R, Ikeda A, Okazaki T, Chiba T, and Watanabe N.
IFN-g is reciprocally involved in the concurrent development of organ-specific autoimmunity in the liver and stomach.
Autoimmunity, 45(2): 186-198, 2012

13. Kayama H, Ueda Y, Sawa Y, Jeon SG, Ma JS, Okumura R, Kubo A, Ishii M, Okazaki T, Murakami M, Yamamoto M, Yagita H, and Takeda K.
Intestinal CX3C chemokine receptor 1high (CX3CR1high) myeloid cells prevent T-cell-dependent colitis.
Proceedings of the National Academy of Sciences of the USA, 109(13): 5010-5015, 2012

14. Chikuma S, Suita N, Okazaki IM, Shibayama S, and Honjo T.
TRIM28 prevents autoinflammatory T cell development in vivo.
Nature Immunology, 13(6): 596-603, 2012

15. Okazaki T, Okazaki IM, Wang J, Sugiura D, Nakaki F, Yoshida T, Kato Y, Fagarasan S, Muramatsu M, Eto T, Hioki K, and Honjo T.
PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice.
Journal of Experimental Medicine, 208(2): 395-407, 2011

16. Aoki N, Kido M, Iwamoto S, Nishiura H, Maruoka R, Tanaka J, Watanabe T, Tanaka Y, Okazaki T, Chiba T, and Watanabe N.
Dysregulated generation of follicular helper T cells in the spleen triggers fatal autoimmune hepatitis in mice.
Gastroenterology, 140(4): 1322-1333, 2011

17. Terawaki S, Chikuma S, Shibayama S, Hayashi T, Yoshida T, Okazaki T, and Honjo T.
Interferon a directly promotes programmed-cell-death-1 transcription and limits the duration of T cell-mediated immunity.
Journal of Immunology, 186(5): 2772-2779,2011

18. Okazaki IM, Okawa K, Kobayashi M, Yoshikawa K, Kawamoto S, Nagaoka H, Shinkura R, Kitawaki Y, Taniguchi H, Natsume T, Iemura S, and Honjo T.
Histone chaperone Spt6 is required for class switch recombination but not somatic hypermutation.
Proceedings of the National Academy of Sciences of the USA, 108(19): 7920-7925, 2011

19. Sakai S, Kawamura I, Okazaki T, Tsuchiya K, Uchiyama R, and Mitsuyama M.
PD-1-PD-L1 pathway impairs T(h)1 immune response in the late stage of infection with Mycobacterium bovis bacillus Calmette-Guérin.
International Immunology, 22(9): 915-925, 2010

20. Kasagi S, Kawano S, Okazaki T, Honjo T, Morinobu A, Hatachi S, Shimatani S, Tanaka Y, Minato N, and Kumagai S.
Anti-PD-1 antibody reduces CD4+PD-1+ T cells and relieves the lupus-like nephritis of NZB/W F1 mice.
Journal of Immunology, 184(5): 2337-2347, 2010

21. Wang J, Okazaki IM, Yoshida T, Chikuma S, Kato Y, Nakaki F, Hiai H, Honjo T, and Okazaki T.
PD-1 deficiency results in the development of fatal myocarditis in MRL mice.
International Immunology, 22(6): 443-452, 2010

22. Hino S, Kabashima K, Kato Y, Yagi H, Nakamura M, Honjo T, Okazaki T, and Tokura Y.
Tumor cell expression of programmed cell death 1 ligand 1 is a prognostic factor for malignant melanoma.
Cancer, 116(7): 1757-1766, 2010

23. Chikuma S, Terawaki S, Hayashi T, Nabeshima R, Yoshida Y, Shibayama S, Okazaki T, and Honjo T.
PD-1-mediated suppression of IL-2 production induces CD8+ T-cell anergy in vivo.
Journal of Immunology, 182(11): 6682-6689, 2009

24. Jiang F, Yoshida T, Nakaki F, Terawaki S, Chikuma S, Kato Y, Okazaki IM, Honjo T, and Okazaki T.
Identification of QTLs that modify peripheral neuropathy in NOD.H2b–Pdcd1–/– mice.
International Immunology, 21(5): 499-509, 2009

25. Sugita S, Usui Y, Horie S, Futagami Y, Aburatani H, Okazaki T, Honjo T, Takeuchi M, and Mochizuki M.
T cell suppression by programmed cell death 1 ligand 1 on retinal pigment epithelium during inflammatory conditions.
Investigative Ophthalmology & Visual Science, Jun;50(6): 2862-70, 2009

26. Kobayashi M, Aida M, Nagaoka H, Begum NA, Kitawaki Y, Nakata M, Stanlie A, Doi T, Kato L, Okazaki IM, Shinkura R, Muramatsu M, Kinoshita K, and Honjo T.
AID-induced decrease in topoisomerase 1 induces DNA structural alteration and DNA cleavage for class switch recombination.
Proceedings of the National Academy of Sciences of the USA, 106(52): 22375-22380, 2009

27. Sabouri Z, Okazaki IM, Shinkura R, Begum N, Nagaoka H, Tsuchimoto D, Nakabeppu Y, and Honjo T.
Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes.
International Immunology, 21(8): 947-955, 2009

28. Shivarov V, Shinkura R, Doi T, Begum NA, Nagaoka H, Okazaki IM, Ito S, Nonaka T, Kinoshita K, and Honjo T.
Molecular mechanism for generation of antibody memory.
Philosophical Transactions of the Royal Society B: Biological Sciences, 364(1517): 569-575, 2009

29. Takai A, Toyoshima T, Uemura M, Kitawaki Y, Marusawa H, Hiai H, Yamada S, Okazaki IM, Honjo T, Chiba T, and Kinoshita K.
A novel mouse model of hepatocarcinogenesis triggered by AID causing deleterious p53 mutations.
Oncogene, 28(4): 469-478, 2009

30. Kido M, Watanabe N, Okazaki T, Akamatsu T, Tanaka J, Saga K, Nishio A, Honjo T, and Chiba T.
Fatal autoimmune hepatitis induced by concurrent loss of naturally arising regulatory T cells and PD-1-mediated signaling.
Gastroenterology, 135(4): 1333-43, 2008

31. Yoshida T, Jiang F, Honjo T, and Okazaki T.
PD-1 deficiency reveals various tissue-specific autoimmunity by H-2b and dose-dependent requirement of H-2g7 for diabetes on NOD background.
Proceedings of the National Academy of Sciences of the USA, 105(9): 3533-3538, 2008

32. Lin DY, Tanaka Y, Iwasaki M, Gittis AG, Su HP, Mikami B, Okazaki T, Honjo T, Minato N, and Garboczi DN.
The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors.
Proceedings of the National Academy of Sciences of the USA, 105(8): 3011-3016, 2008

33. Green KA, Okazaki T, Honjo T, Cook WJ, and Green WR.
The programmed death-1 and interleukin-ao pathway play a down-modulatory role in LP-BM5 retrovirus-induced murine immunodeficiency syndrome.
Journal of Virology, 82(5): 2456-2469, 2008

34. Morisawa T, Marusawa H, Ueda Y, Iwai A, Okazaki IM, Honjo T, and Chiba T.
Organ-specific profiles of genetic changes in cancers caused by activation-induced cytidine deaminase expression.
International Journal of Cancer, 123(12): 2735-2740, 2008

35. Okazaki T and Honjo T.
PD-1 and PD-1 ligands: from discovery to clinical application.
International Immunology, 19(7): 813-824, 2007

36. Terawaki S, Tanaka Y, Nagakura T, Hayashi T, Shibayama S, Muroi K, Okazaki T, Mikami B, Garboczi DN, Honjo T, and Minato N.
Specific and high-affinity binding of tetramerized PD-L1 extracellular domain to PD-1-expressing cells: possible application to enhance T cell function.
International Immunology, 19(7): 881-890, 2007

37. Hamanishi J, Mandai M, Iwasaki M, Okazaki T, Tanaka Y, Yamaguchi K, Higuchi T, Yagi H, Takakura K, Minato N, Honjo T, and Fujii S.
Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer.
Proceedings of the National Academy of Sciences of the USA, 104(9): 3360-3365, 2007

38. Okazaki IM, Kotani A, and Honjo T.
Role of AID in tumorigenesis.
Advances in Immunology, 94: 245-273, 2007

39. Endo Y, Marusawa H, Kinoshita K, Morisawa T, Sakurai T, Okazaki IM, Watashi K, Shimotohno K, Honjo T, and Chiba T.
Expression of activation-induced cytidine deaminase in human hepatocytes via NF-kappaB signaling.
Oncogene, 26(38): 5587-5595, 2007

40. Matsumoto Y, Marusawa H, Kinoshita K, Endo Y, Kou T, Morisawa T, Azuma T, Okazaki IM, Honjo T, and Chiba T.
Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium.
Nature Medicine, 13(4): 470-476, 2007

41. Shinkura R, Okazaki IM, Muto T, Begum NA, and Honjo T.
Regulation of AID function in vivo.
Advances in Experimental Medicine and Biology, 596: 71-81, 2007

42. Kotani A, Kakazu N, Tsuruyama T, Okazaki IM, Muramatsu M, Kinoshita K, Nagaoka H, Yabe D, and Honjo T.
Activation-induced cytidine deaminase (AID) promotes B cell lymphomagenesis in Emu-cmyc transgenic mice.
Proceedings of the National Academy of Sciences of the USA, 104(5): 1616-1620, 2007

43. Kou T, Marusawa H, Kinoshita K, Endo Y, Okazaki IM, Ueda Y, Kodama Y, Haga H, Ikai I, and Chiba T.
Expression of activation-induced cytidine deaminase in human hepatocytes during hepatocarcinogenesis.
International Journal of Cancer, 120(3): 469-476, 2007

44. Okazaki T and Honjo T.
The PD-1-PD-L pathway and immunological tolerance.
Trends in Immunology, 27(4): 195-201, 2006

45. Okazaki T and Honjo T.
Rejuvenating exhausted T cells during chronic viral infection.
Cell, 124(3): 459-461, 2006

46. Muto T, Okazaki IM, Yamada S, Tanaka Y, Kinoshita K, Muramatsu M, Nagaoka H, and Honjo T.
Negative regulation of activation-induced cytidine deaminase in B cells.
Proceedings of the National Academy of Sciences of the USA, 103(8): 2752-2757, 2006

47. Okazaki T, Otaka Y, Wang J, Hiai H, Takai T, Ravetch JV and Honjo T.
Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b-/-Pdcd1-/- mice.
Journal of Experimental Medicine, 202(12): 1643-1648, 2005

48. Kobayashi M, Kawano S, Hatachi S, Kurimoto C, Okazaki T, Iwai Y, Honjo T, Tanaka Y, Minato N, Komori T, Maeda S, and Kumagai S.
Enhanced expression of programmed death-1 (PD-1)/PD-L1 in salivary glands of patients with Sjogren's syndrome.
Journal of Rheumatology, 32(11): 2156-2163, 2005

49. Okazaki T and Honjo T.
Pathogenic roles of cardiac autoantibodies in dilated cardiomyopathy.
Trends in Molecular Medicine, 11(5): 322-326, 2005

50. Wang J, Yoshida T, Nakaki F, Hiai H, Okazaki T, and Honjo T.
Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes.
Proceedings of the National Academy of Sciences of the USA, 102(33): 11823-11828, 2005

51. Okazaki T and Wang J.
PD-1/PD-L pathway and autoimmunity.
Autoimmunity, 38(7): 353-357, 2005

52. Probst HC, McCoy K, Okazaki T, Honjo T, and van den Broek M.
Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4.
Nature Immunology, 6(3): 280-286, 2005

53. Kotani A, Okazaki IM, Muramatsu M, Kinoshita K, Begum NA, Nakajima T, Saito H, and Honjo T.
A target selection of somatic hypermutations is regulated similarly between T and B cells upon activation-induced cytidine deaminase expression.
Proceedings of the National Academy of Sciences of the USA, 102(12): 4506-11, 2005

54. Okazaki T, Tanaka Y, Nishio R, Mitsuiye T, Mizoguchi A, Wang J, Ishida M, Hiai H, Matsumori A, Minato N, and Honjo T.
Autoantibodies against cardiac troponin I are responsible for the dilated cardiomyopathy in PD-1 deficient mice.
Nature Medicine, 9(12): 1477-1483, 2003

55. Iwai Y, Terawaki S, Ikegawa M, Okazaki T, and Honjo T.
PD-1 inhibits antiviral immunity at the effector phase in the liver.
Journal of Experimental Medicine, 198(1): 39-50, 2003

56. Okazaki IM, Hiai H, Kakazu N, Yamada S, Muramatsu M, Kinoshita K, and Honjo T.
Constitutive expression of AID leads to tumorigenesis.
Journal of Experimental Medicine, 197(9): 1173-1181, 2003

57. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, and Minato N.
Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade.
Proceedings of the National Academy of Sciences of the USA, 99(19): 12293-12297, 2002

58. Kanazawa N, Okazaki T, Nishimura H, Tashiro K, Inaba K, and Miyachi Y.
DCIR acts as an inhibitory receptor depending on its immunoreceptor tyrosine-based inhibitory motif.
Journal of Investigative Dermatology, 118(2): 261-266, 2002

59. Okazaki T, Iwai Y, and Honjo T.
New regulatory co-receptors: inducible co-stimulator and PD-1.
Current Opinion in Immunology, 14(6): 779-782, 2002

60. Ishida M, Iwai Y, Tanaka Y, Okazaki T, Freeman GJ, Minato N, and Honjo T.
Differential expression of PD-L1 and PD-L2, ligands for an inhibitory receptor PD-1, in the cells of lymphohematopoietic tissues.
Immunology Letters, 84(1): 57-62, 2002

61. Iwai Y, Okazaki T, Nishimura H, Kawasaki A, Yagita H, and Honjo T.
Microanatomical localization of PD-1 in human tonsils.
Immunology Letters, 83(3): 215-220, 2002

62. Yoshikawa K, Okazaki IM, Eto T, Kinoshita K, Muramatsu M, Nagaoka H, and Honjo T.
AID enzyme-induced hypermutation in an actively transcribed gene in fibroblasts.
Science. 296(5575): 2033-2036, 2002

63. Okazaki IM, Kinoshita K, Muramatsu M, Yoshikawa K, and Honjo T.
The AID enzyme induces class switch recombination in fibroblasts.
Nature. 416(6878): 340-345, 2002

64. Okazaki T, Maeda A, Nishimura H, Kurosaki T, and Honjo T.
PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine.
Proceedings of the National Academy of Sciences of the USA, 98(24): 13866-133871, 2001

65. Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, Iwai Y, Long AJ, Brown JA, Nunes R, Greenfield EA, Bourque K, Boussiotis VA, Carter LL, Carreno BM, Malenkovich N, Nishimura H, Okazaki T, Honjo T, Sharpe AH, and Freeman GJ.
PD-L2 is a second ligand for PD-1 and inhibits T cell activation.
Nature Immunology, 2(3): 261-268, 2001

66. Nishimura H, Okazaki T, Tanaka Y, Nakatani K, Hara M, Matsumori A, Sasayama S, Mizoguchi A, Hiai H, Minato N, and Honjo T.
Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice.
Science, 291(5502): 319-322, 2001

67. Okazaki T, Iwai Y, Nishimura H, and Honjo T.
The regulation of PD-1/PD-L1 pathway and autoimmune diseases.
In: Activating and inhibitory immunoglobulin-like receptors, Eds. Cooper, M.D., Takai, T. and Ravetch, J.V. (Springer-Verlag, Tokyo), 211-214, 2001

68. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, and Honjo T.
Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.
Journal of Experimental Medicine, 192(7): 1027-1034, 2000

69. Mandelboim O, Kent S, Davis DM, Wilson SB, Okazaki T, Jackson R, Hafler D, and Strominger JL.
Natural killer activating receptors trigger interferon gamma secretion from T cells and natural killer cells.
Proceedings of the National Academy of Sciences of the USA, 95(7): 3798-3803, 1998

70. Minoguchi S, Taniguchi Y, Kato H, Okazaki T, Strobl LJ, Zimber-Strobl U, Bornkamm GW, and Honjo T.
RBP-L, a transcription factor related to RBP-Jkappa.
Molecular and Cellular Biology, 17(5): 2679-2687, 1997

71. Satoh N, Ogawa Y, Katsuura G, Tsuji T, Masuzaki H, Hiraoka J, Okazaki T, Tamaki M, Hayase M, Yoshimasa Y, Nishi S, Hosoda K, and Nakao K.
Pathophysiological significance of the obese gene product, leptin, in ventromedial hypothalamus (VMH)-lesioned rats: evidence for loss of its satiety effect in VMH-lesioned rats.
Endocrinology, 138(3): 947-954, 1997

72. Okazaki T, Ogawa Y, Tamura N, Mori K, Isse N, Aoki T, Rochelle JM, Taketo MM, Seldin MF, and Nakao K.
Genomic organization, expression, and chromosomal mapping of the mouse adrenomedullin gene.
Genomics, 37(3): 395-399, 1996

73. Takaya K, Ogawa Y, Isse N, Okazaki T, Satoh N, Masuzaki H, Mori K, Tamura N, Hosoda K, and Nakao K.
Molecular cloning of rat leptin receptor isoform complementary DNAs--identification of a missense mutation in Zucker fatty (fa/fa) rats.
Biochemical and Biophysical Research Communications, 225(1): 75-83, 1996

74. Isse N, Ogawa Y, Tamura N, Masuzaki H, Mori K, Okazaki T, Satoh N, Shigemoto M, Yoshimasa Y, Nishi S, Hosoda K, Inazawa J, and Nakao, K.
Structural organization and chromosomal assignment of the human obese gene.
Journal of Biological Chemistry, 270(46): 27728-27733, 1995

75. Ogawa Y, Masuzaki H, Isse N, Okazaki T, Mori K, Shigemoto M, Satoh N, Tamura N, Hosoda K, Yoshimasa Y, Jingami H, Kawada T, and Nakao K.
Molecular cloning of rat obese cDNA and augmented gene expression in genetically obese Zucker fatty (fa/fa) rats.
Journal of Clinical Investigation, 96(3): 1647-1652, 1995

76. Masuzaki H, Ogawa Y, Isse N, Satoh N, Okazaki T, Shigemoto M, Mori K, Tamura N, Hosoda K, Yoshimasa Y, Jingami H, Kawada T, and Nakao K.
Human obese gene expression. Adipocyte-specific expression and regional differences in the adipose tissue.
Diabetes, 44(7): 855-858, 1995