Effect of genetic background on Ea(d) transgene-mediated protection from murine lupus

Article Article scientifique Article Effect of genetic background on Ea(d) transgene-mediated protection from murine lupus eng 1998 author Iwamoto Masahiro 28036 author Ibnou-Zekri Nabila 47032 author Kobayakawa Takatoshi author Izui Shozo 25552 241-248 10.1006/jaut.1998.0196 9693972 0896-8411 https://www.sciencedirect.com/science/article/pii/S0896841198901962 The expression of a transgenic encoding the I-E alpha-chain, Ea(d), is highly effective in the protection from systemic lupus erythematosus (SLE) in BXSB and (MRL x BXSB)F1 male mice, in which a mutant gene, Yaa (Y-linked autoimmune acceleration), plays a critical role. To gain further insight into the protective role of the Ea(d) transgene, we compared the effect of the transgene in two additional lupus-prone (NZB x BXSB)F1 and (NZW x BXSB)F1 hybrid mice, in which both F1 female mice develop typical SLE in the absence of the Yaa gene and their F1 males bearing the Yaa gene develop a more accelerated form of SLE. Comparative analysis of the clinical development of SLE in these F1 hybrid mice showed that Ea(d) transgene expression was much more effective in the protection from SLE occurring in the F1 females than in their male counterparts. Our results indicate that the Ea(d) transgene is capable of preventing SLE by inhibiting autoimmune responses, independently of the Yaa gene-accelerating effect, and that its protective capacity is strongly influenced by the genetic susceptibility to SLE in individual strains of lupus-prone mice. In addition, this autoimmune inhibitory effect was shown to be selective for IgG, but not IgM, anti-DNA autoantibody production, and is more specific for anti-gp70 autoantibody than for anti-DNA autoantibody. These results favour the hypothesis that the transgene expression may lead to the modulation of self-peptide presentation, thereby preventing excessive T-cell-dependent activation of autoreactive B cells. Animals Antigen-Antibody Complex/blood Autoantibodies/blood Autoimmunity/ genetics Chimera DNA/immunology Female Gene Therapy/ methods Glycoproteins/blood Histocompatibility Antigens Class II/biosynthesis/genetics/ therapeutic use Linkage (Genetics) Lupus Nephritis/genetics/ prevention & control Male Mice Mice, Inbred NZB Mice, Transgenic Sex Chromosome Aberrations Sex Factors Transgenes Y Chromosome Dewey 616.07 137 Département de pathologie et immunologie 21F false Journal of autoimmunity 11 3 b93f2fb5-8adb-40a8-b45a-a4be263ada4d Article (Published version) Restricted file1.pdf 231455 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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Effect of genetic background on Ea(d) transgene-mediated protection from murine lupus	Journal of autoimmunity			1998	492	1

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Iwamoto, Masahiro