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Gene Review

Tnfrsf25  -  tumor necrosis factor receptor superfamily...

Mus musculus

Synonyms: APO-3, DDR3, DR3, LARD, TR3, ...
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Disease relevance of Tnfrsf25


High impact information on Tnfrsf25

  • Our data suggest that interaction of TL1A with DR3 promotes T cell expansion during an immune response, whereas TR6 has an opposing effect [4].
  • TL1A induces NF-kappaB activation and apoptosis in DR3-expressing cell lines, while TR6-Fc protein antagonizes these signaling events [4].
  • DR3 is a death domain-containing receptor that is upregulated during T cell activation and whose overexpression induces apoptosis and NF-kappaB activation in cell lines [4].
  • In fibroblast strains derived from these embryos, the TNF receptors, Fas/Apo1, and DR3 were able to activate the Jun N-terminal kinase and to trigger IkappaB alpha phosphorylation and degradation [5].
  • Mice expressing transgenes for one or both of the HLA class II molecules positively associated with MG (DQ8 and DR3) developed EAMG [2].

Biological context of Tnfrsf25


Anatomical context of Tnfrsf25

  • Fifteen spontaneous immunocytomas originating in the ileocecal lymph nodes of Lou/C/Wsl rats were studied by means of electron microscopy [8].
  • To examine this possibility, we generated a panel of B-cell transfectants whose DR molecule is composed of either the DR alpha or the E alpha chain paired with a DR3 beta chain [9].
  • In cultured keratinocytes, 9-cis retinoic acid (9cRA), a panagonist for RXR and retinoic acid receptor (RAR), and an RXR-selective agonist, SR11237, synergized with D3 to activate DR3 via endogenous as well as overexpressed VDR-RXR, whereas both of these RXR agonists alone were ineffective [10].
  • There were no strain differences in DR3 mRNA expression in the ventral striatum or prefrontal cortex, nor were there differences in D1R binding in the ventral striatum [11].
  • We determined whether this DR3 was the optimal and/or only recognition sequence, by PCR-mediated binding site selection with reticulocyte lysate-expressed hVDR and mRXRalpha, and a pool of random sequences [12].

Associations of Tnfrsf25 with chemical compounds

  • Scanning a DRB3*0101 (DR52a)-restricted epitope cross-presented by DR3: overlapping natural and artificial determinants in the human acetylcholine receptor [13].
  • Surprisingly, despite the 9 sequence differences in DRbeta between DR52a and DR3, merely reducing the bulk of the peptide's p1 anchor residue (Trp149-->Phe) allowed maximal cross-presentation to both T cells by DR3 (which has Val86 instead of Gly) [13].
  • Furthermore, expression of RXR mutated in transactivation domain AF-2 inhibited endogenous VDR-RXR activity over DR3 [10].
  • In vitro, RXR and VDR-specific antibodies identified endogenous RXR and VDR bound to a vitamin D3-responsive element (DR3) as heterodimers (VDR-RXR) [10].
  • Dietary Lard intake did not significantly affect concentrations of plasma triglyceride although those of plasma cholesterol were significantly increased (P<0.05) [14].

Other interactions of Tnfrsf25

  • The pre-T-cell receptor-mediated checkpoint, which is dependent on TNFR signaling, is also unaffected in DR3-deficient mice [6].

Analytical, diagnostic and therapeutic context of Tnfrsf25

  • In both ELISA and cytotoxicity one reacted with all lymphoblastoid cell lines tested, one reacted with all except two that were DR7 homozygous and the third reacted strongly only with cells that were DR3 [15].
  • From titration analysis and quantitative absorption studies the PL2 determinant was found to be expressed at quantitatively different levels in the following order: DR7 greater than DRw11, DRw14 greater than DRw13 greater than DR3 greater than DR2 [16].
  • These data, together with information for other mouse strains, demonstrate that MHC (human and murine) and non-MHC genes contribute to the outcome of TSHR-DNA vaccination and indicate the potential value of DR3 transgenic mice for dissecting immune responses to the TSHR [17].


  1. Role of TL1A and its receptor DR3 in two models of chronic murine ileitis. Bamias, G., Mishina, M., Nyce, M., Ross, W.G., Kollias, G., Rivera-Nieves, J., Pizarro, T.T., Cominelli, F. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  2. Mapping myasthenia gravis-associated T cell epitopes on human acetylcholine receptors in HLA transgenic mice. Yang, H., Goluszko, E., David, C., Okita, D.K., Conti-Fine, B., Chan, T.S., Poussin, M.A., Christadoss, P. J. Clin. Invest. (2002) [Pubmed]
  3. Immunogenetics of experimental autoimmune myasthenia gravis. Christadoss, P. Crit. Rev. Immunol. (1989) [Pubmed]
  4. TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator. Migone, T.S., Zhang, J., Luo, X., Zhuang, L., Chen, C., Hu, B., Hong, J.S., Perry, J.W., Chen, S.F., Zhou, J.X., Cho, Y.H., Ullrich, S., Kanakaraj, P., Carrell, J., Boyd, E., Olsen, H.S., Hu, G., Pukac, L., Liu, D., Ni, J., Kim, S., Gentz, R., Feng, P., Moore, P.A., Ruben, S.M., Wei, P. Immunity (2002) [Pubmed]
  5. Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. Varfolomeev, E.E., Schuchmann, M., Luria, V., Chiannilkulchai, N., Beckmann, J.S., Mett, I.L., Rebrikov, D., Brodianski, V.M., Kemper, O.C., Kollet, O., Lapidot, T., Soffer, D., Sobe, T., Avraham, K.B., Goncharov, T., Holtmann, H., Lonai, P., Wallach, D. Immunity (1998) [Pubmed]
  6. DR3 regulates negative selection during thymocyte development. Wang, E.C., Thern, A., Denzel, A., Kitson, J., Farrow, S.N., Owen, M.J. Mol. Cell. Biol. (2001) [Pubmed]
  7. Transrepression by a liganded nuclear receptor via a bHLH activator through co-regulator switching. Murayama, A., Kim, M.S., Yanagisawa, J., Takeyama, K., Kato, S. EMBO J. (2004) [Pubmed]
  8. Rat ileocecal immunocytoma. An ultrastructural study with special attention to the presence of viral particles. Burtonboy, G., Beckers, A., Rodhain, J., Bazin, H., Lamy, M.E. J. Natl. Cancer Inst. (1978) [Pubmed]
  9. Replacement of the DR alpha chain with the E alpha chain enhances presentation of Mycoplasma arthritidis superantigen by the human class II DR molecule. Sawada, T., Pergolizzi, R., Ito, K., Silver, J., Atkin, C., Cole, B.C., Chang, M.D. Infect. Immun. (1995) [Pubmed]
  10. Retinoid X receptor-specific ligands synergistically upregulate 1, 25-dihydroxyvitamin D3-dependent transcription in epidermal keratinocytes in vitro and in vivo. Li, X.Y., Xiao, J.H., Feng, X., Qin, L., Voorhees, J.J. J. Invest. Dermatol. (1997) [Pubmed]
  11. C57BL/6J mice exhibit reduced dopamine D3 receptor-mediated locomotor-inhibitory function relative to DBA/2J mice. McNamara, R.K., Levant, B., Taylor, B., Ahlbrand, R., Liu, Y., Sullivan, J.R., Stanford, K., Richtand, N.M. Neuroscience (2006) [Pubmed]
  12. Identification of DNA sequences that bind retinoid X receptor-1,25(OH)2D3-receptor heterodimers with high affinity. Colnot, S., Lambert, M., Blin, C., Thomasset, M., Perret, C. Mol. Cell. Endocrinol. (1995) [Pubmed]
  13. Scanning a DRB3*0101 (DR52a)-restricted epitope cross-presented by DR3: overlapping natural and artificial determinants in the human acetylcholine receptor. Nagvekar, N., Corlett, L., Jacobson, L.W., Matsuo, H., Chalkley, R., Driscoll, P.C., Deshpande, S., Spack, E.G., Willcox, N. J. Immunol. (1999) [Pubmed]
  14. Effects of genetic and diet-induced obesity on lipid metabolism. Libinaki, R., Heffernan, M., Jiang, W.J., Ogru, E., Ignjatovic, V., Gianello, R., Trickey, L., Taylor, M., Ng, F. IUBMB Life (1999) [Pubmed]
  15. Serological biochemical and functional characterisation of three different HLA-DR monoclonal antibodies derived from C57BL6 mice. Sachs, J.A., Fernandez, N., Kurpisz, M., Okoye, R., Ogilvie, J., Awad, J., Labeta, M., Festenstein, H. Tissue Antigens (1986) [Pubmed]
  16. A new supertypic HLA class II determinant (PL2) differentially expressed with DR7, DRw11(5), DRw13(w6), DRw14(w6), DR3, and DR2 and biochemically localized to DR7 molecules. Horibe, K., Knowles, R.W., Dupont, B. Hum. Immunol. (1986) [Pubmed]
  17. Thyrotropin receptor-DNA vaccination of transgenic mice expressing HLA-DR3 or HLA-DQ6b. Pichurin, P., Chen, C.R., Pichurina, O., David, C., Rapoport, B., McLachlan, S.M. Thyroid (2003) [Pubmed]
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