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Gene Review

Pdcd1  -  programmed cell death 1

Mus musculus

Synonyms: Ly101, PD-1, Pd1, Pdc1, Programmed cell death protein 1, ...
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Disease relevance of Pdcd1


Psychiatry related information on Pdcd1


High impact information on Pdcd1


Chemical compound and disease context of Pdcd1


Biological context of Pdcd1

  • Using NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes, we screened diabetes-susceptible loci by genetic linkage analysis [15].
  • Collectively, it is suggested that PD-1 is involved in the maintenance of peripheral self-tolerance by serving as a negative regulator of immune responses [16].
  • We then constructed a eukaryotic expression plasmid (pPD-1A) that expresses the extracellular domain of murine PD-1 (sPD-1). sPD-1 could bind PD-1 ligands, block PD-Ls-PD-1 interactions, and enhance the cytotoxicity of tumor-specific CTL [17].
  • Our results suggest that PD-1 deficiency reduces osteoclastogenesis resulting in an osteopetrotic phenotype [18].
  • Both trabecular and cortical bone mineral densities of tibia were significantly increased, as observed in peripheral quantitative computed tomography (pQCT), at 12 weeks of age in PD-1-/- mice [18].

Anatomical context of Pdcd1


Associations of Pdcd1 with chemical compounds

  • Programmed death-1 (PD-1) is an immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptor expressed upon T cell activation [4].
  • CONCLUSION: Blockade of the PD-1/B7-H1 pathway with sPD-1 may be a promising strategy for immunotherapy for hepatocarcinoma [23].
  • Omega-3 fatty acid docosahexaenoic acid is converted to potent resolvins (Rv) and protectin D1 (PD1), two newly identified families of natural mediators of resolution of inflammation [24].
  • The rank order at 1- to 10-ng dose was PD1 approximately PD1 methyl ester >> Delta15-trans-PD1 > 10S,17S-diHDHA (isomer I) [25].
  • Programmed cell death is required for palate shelf fusion and is regulated by retinoic acid [26].

Physical interactions of Pdcd1


Regulatory relationships of Pdcd1

  • We found that CH27 expressed B7RP-1 and PD-L1 whereas the T cell lines expressed ICOS and PD-1 [27].
  • As expected, an increase in the production of IL-2 was seen when blocking antibodies for PD-1 were used [27].
  • Programmed cell death of embryonic motoneurons triggered through the Fas death receptor [28].
  • These data indicate that PD-1 ligation down-regulates GVHD through modulation of IFN-gamma production and suggest a novel therapeutic target for inhibiting GVHD lethality [29].
  • We further report for the first time that engagement of PD-1 inhibits cell cycle progression in primary B cells and that modulation of PD-1 expression by CpG or IL-4 significantly reverses such inhibition [30].

Other interactions of Pdcd1

  • Cooperative B7-1/2 (CD80/CD86) and B7-DC costimulation of CD4+ T cells independent of the PD-1 receptor [31].
  • Costimulation with soluble anti-CD28 mAb can overcome PD-1-mediated inhibition by augmenting IL-2 production [4].
  • Programmed death-1 (PD-1) receptor, an inhibitory costimulatory molecule found on activated T cells, has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance [1].
  • Programmed death-1 (PD-1), an inhibitory receptor up-regulated on activated T cells, has been shown to play a critical immunoregulatory role in peripheral tolerance, but its role in alloimmune responses is poorly understood [32].
  • These results suggest a unique role for B7-DC in the regulation of asthmatic response through an IFN-gamma-dependent, but PD-1-independent, mechanism [33].

Analytical, diagnostic and therapeutic context of Pdcd1

  • Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes [15].
  • We examined the expression and functions of PD-1 and its ligands in experimental cardiac allograft rejection [34].
  • These data show that when combined with limited immunosuppression, or in the context of submaximal TCR or costimulatory signals, targeting of PD-1 can block allograft rejection and modulate T and B cell-dependent pathologic immune responses in vivo [34].
  • Notably, we found that even in persistently infected mice that were lacking CD4 T-cell help, blockade of the PD-1/PD-L1 inhibitory pathway had a beneficial effect on the 'helpless' CD8 T cells, restoring their ability to undergo proliferation, secrete cytokines, kill infected cells and decrease viral load [35].
  • By comparative molecular modeling and site-directed mutagenesis, we found that nonconserved residues between these ligands on the A'GFCC'C" face mediate interaction with PD-1 [22].


  1. The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice. Ansari, M.J., Salama, A.D., Chitnis, T., Smith, R.N., Yagita, H., Akiba, H., Yamazaki, T., Azuma, M., Iwai, H., Khoury, S.J., Auchincloss, H., Sayegh, M.H. J. Exp. Med. (2003) [Pubmed]
  2. Differential role of programmed death-ligand 1 and programmed death-ligand 2 in regulating the susceptibility and chronic progression of experimental autoimmune encephalomyelitis. Zhu, B., Guleria, I., Khosroshahi, A., Chitnis, T., Imitola, J., Azuma, M., Yagita, H., Sayegh, M.H., Khoury, S.J. J. Immunol. (2006) [Pubmed]
  3. Blockade of B7-H1 suppresses the development of chronic intestinal inflammation. Kanai, T., Totsuka, T., Uraushihara, K., Makita, S., Nakamura, T., Koganei, K., Fukushima, T., Akiba, H., Yagita, H., Okumura, K., Machida, U., Iwai, H., Azuma, M., Chen, L., Watanabe, M. J. Immunol. (2003) [Pubmed]
  4. PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2. Carter, L., Fouser, L.A., Jussif, J., Fitz, L., Deng, B., Wood, C.R., Collins, M., Honjo, T., Freeman, G.J., Carreno, B.M. Eur. J. Immunol. (2002) [Pubmed]
  5. Programmed cell death (apoptosis) in Alzheimer's disease and Creutzfeldt-Jakob disease. Jesionek-Kupnicka, D., Buczyński, J., Kordek, R., Sobów, T., Kłoszewska, I., Papierz, W., Liberski, P.P. Folia neuropathologica / Association of Polish Neuropathologists and Medical Research Centre, Polish Academy of Sciences. (1997) [Pubmed]
  6. Overexpression of wild-type presenilin 2 or its familial Alzheimer's disease-associated mutant does not induce or increase susceptibility to apoptosis in different cell lines. Gamliel, A., Teicher, C., Hartmann, T., Beyreuther, K., Stein, R. Neuroscience (2003) [Pubmed]
  7. Programmed cell death in extraocular muscle tendon/sclera precursors. Sulik, K.K., Dehart, D.B., Johnson, C.S., Ellis, S.L., Chen, S.Y., Dunty, W.C., Zucker, R.M. Mol. Vis. (2001) [Pubmed]
  8. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Okazaki, T., Tanaka, Y., Nishio, R., Mitsuiye, T., Mizoguchi, A., Wang, J., Ishida, M., Hiai, H., Matsumori, A., Minato, N., Honjo, T. Nat. Med. (2003) [Pubmed]
  9. Mitochondrial endonuclease G is important for apoptosis in C. elegans. Parrish, J., Li, L., Klotz, K., Ledwich, D., Wang, X., Xue, D. Nature (2001) [Pubmed]
  10. Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Joza, N., Susin, S.A., Daugas, E., Stanford, W.L., Cho, S.K., Li, C.Y., Sasaki, T., Elia, A.J., Cheng, H.Y., Ravagnan, L., Ferri, K.F., Zamzami, N., Wakeham, A., Hakem, R., Yoshida, H., Kong, Y.Y., Mak, T.W., Zúñiga-Pflücker, J.C., Kroemer, G., Penninger, J.M. Nature (2001) [Pubmed]
  11. Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB. Wang, C.Y., Cusack, J.C., Liu, R., Baldwin, A.S. Nat. Med. (1999) [Pubmed]
  12. Interleukin-2 programs mouse alpha beta T lymphocytes for apoptosis. Lenardo, M.J. Nature (1991) [Pubmed]
  13. Facilitation of beta selection and modification of positive selection in the thymus of PD-1-deficient mice. Nishimura, H., Honjo, T., Minato, N. J. Exp. Med. (2000) [Pubmed]
  14. Programmed cell death in the pathogenesis of murine IDDM: resistance to apoptosis induced in lymphocytes by cyclophosphamide. Colucci, F., Cilio, C.M., Lejon, K., Gonçalves, C.P., Bergman, M.L., Holmberg, D. J. Autoimmun. (1996) [Pubmed]
  15. Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes. Wang, J., Yoshida, T., Nakaki, F., Hiai, H., Okazaki, T., Honjo, T. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  16. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Nishimura, H., Nose, M., Hiai, H., Minato, N., Honjo, T. Immunity (1999) [Pubmed]
  17. Blocking programmed death-1 ligand-PD-1 interactions by local gene therapy results in enhancement of antitumor effect of secondary lymphoid tissue chemokine. He, Y.F., Zhang, G.M., Wang, X.H., Zhang, H., Yuan, Y., Li, D., Feng, Z.H. J. Immunol. (2004) [Pubmed]
  18. The deficiency of immunoregulatory receptor PD-1 causes mild osteopetrosis. Nagahama, K., Aoki, K., Nonaka, K., Saito, H., Takahashi, M., Varghese, B.J., Shimokawa, H., Azuma, M., Ohya, K., Ohyama, K. Bone (2004) [Pubmed]
  19. BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1. Watanabe, N., Gavrieli, M., Sedy, J.R., Yang, J., Fallarino, F., Loftin, S.K., Hurchla, M.A., Zimmerman, N., Sim, J., Zang, X., Murphy, T.L., Russell, J.H., Allison, J.P., Murphy, K.M. Nat. Immunol. (2003) [Pubmed]
  20. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. Freeman, G.J., Long, A.J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L.J., Malenkovich, N., Okazaki, T., Byrne, M.C., Horton, H.F., Fouser, L., Carter, L., Ling, V., Bowman, M.R., Carreno, B.M., Collins, M., Wood, C.R., Honjo, T. J. Exp. Med. (2000) [Pubmed]
  21. Expression of programmed death 1 ligands by murine T cells and APC. Yamazaki, T., Akiba, H., Iwai, H., Matsuda, H., Aoki, M., Tanno, Y., Shin, T., Tsuchiya, H., Pardoll, D.M., Okumura, K., Azuma, M., Yagita, H. J. Immunol. (2002) [Pubmed]
  22. Molecular modeling and functional mapping of B7-H1 and B7-DC uncouple costimulatory function from PD-1 interaction. Wang, S., Bajorath, J., Flies, D.B., Dong, H., Honjo, T., Chen, L. J. Exp. Med. (2003) [Pubmed]
  23. Blockade of B7-H1 with sPD-1 improves immunity against murine hepatocarcinoma. He, L., Zhang, G., He, Y., Zhu, H., Zhang, H., Feng, Z. Anticancer Res. (2005) [Pubmed]
  24. Resolvin d series and protectin d1 mitigate acute kidney injury. Duffield, J.S., Hong, S., Vaidya, V.S., Lu, Y., Fredman, G., Serhan, C.N., Bonventre, J.V. J. Immunol. (2006) [Pubmed]
  25. Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes. Serhan, C.N., Gotlinger, K., Hong, S., Lu, Y., Siegelman, J., Baer, T., Yang, R., Colgan, S.P., Petasis, N.A. J. Immunol. (2006) [Pubmed]
  26. Programmed cell death is required for palate shelf fusion and is regulated by retinoic acid. Cuervo, R., Valencia, C., Chandraratna, R.A., Covarrubias, L. Dev. Biol. (2002) [Pubmed]
  27. Interaction of B7RP-1 with ICOS negatively regulates antigen presentation by B cells. Wahl, P., Schoop, R., Horan, T.P., Yoshinaga, S.K., Wüthrich, R.P. Inflammation (2003) [Pubmed]
  28. Programmed cell death of embryonic motoneurons triggered through the Fas death receptor. Raoul, C., Henderson, C.E., Pettmann, B. J. Cell Biol. (1999) [Pubmed]
  29. Blockade of programmed death-1 engagement accelerates graft-versus-host disease lethality by an IFN-gamma-dependent mechanism. Blazar, B.R., Carreno, B.M., Panoskaltsis-Mortari, A., Carter, L., Iwai, Y., Yagita, H., Nishimura, H., Taylor, P.A. J. Immunol. (2003) [Pubmed]
  30. Suppression of expression and function of negative immune regulator PD-1 by certain pattern recognition and cytokine receptor signals associated with immune system danger. Zhong, X., Bai, C., Gao, W., Strom, T.B., Rothstein, T.L. Int. Immunol. (2004) [Pubmed]
  31. Cooperative B7-1/2 (CD80/CD86) and B7-DC costimulation of CD4+ T cells independent of the PD-1 receptor. Shin, T., Kennedy, G., Gorski, K., Tsuchiya, H., Koseki, H., Azuma, M., Yagita, H., Chen, L., Powell, J., Pardoll, D., Housseau, F. J. Exp. Med. (2003) [Pubmed]
  32. Role of the programmed death-1 pathway in regulation of alloimmune responses in vivo. Sandner, S.E., Clarkson, M.R., Salama, A.D., Sanchez-Fueyo, A., Domenig, C., Habicht, A., Najafian, N., Yagita, H., Azuma, M., Turka, L.A., Sayegh, M.H. J. Immunol. (2005) [Pubmed]
  33. B7-DC regulates asthmatic response by an IFN-gamma-dependent mechanism. Matsumoto, K., Inoue, H., Nakano, T., Tsuda, M., Yoshiura, Y., Fukuyama, S., Tsushima, F., Hoshino, T., Aizawa, H., Akiba, H., Pardoll, D., Hara, N., Yagita, H., Azuma, M., Nakanishi, Y. J. Immunol. (2004) [Pubmed]
  34. Programmed death-1 targeting can promote allograft survival. Ozkaynak, E., Wang, L., Goodearl, A., McDonald, K., Qin, S., O'Keefe, T., Duong, T., Smith, T., Gutierrez-Ramos, J.C., Rottman, J.B., Coyle, A.J., Hancock, W.W. J. Immunol. (2002) [Pubmed]
  35. Restoring function in exhausted CD8 T cells during chronic viral infection. Barber, D.L., Wherry, E.J., Masopust, D., Zhu, B., Allison, J.P., Sharpe, A.H., Freeman, G.J., Ahmed, R. Nature (2006) [Pubmed]
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