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1.
Genes Immun ; 11(8): 649-59, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20861860

RESUMO

Theiler's murine encephalomyelitis virus-induced demyelination (TMEVD) and experimental allergic encephalomyelitis (EAE) are the principal animal models of multiple sclerosis (MS). Previously, we provided evidence that Tmevd2 and Eae3 may represent either a shared susceptibility locus or members of a gene complex controlling susceptibility to central nervous system inflammatory demyelinating disease. To explore the genetic relationship between Tmevd2 and Eae3, we generated a D2.C-Tmevd2 interval-specific congenic (ISC) line and three overlapping interval-specific recombinant congenic (ISRC) lines in which the Tmevd2-resistant allele from BALB/cByJ was introgressed onto the TMEVD-susceptible DBA/2J background. These mice, all H2(d), were studied for susceptibility to EAE elicited by immunization with proteolipid protein peptide 180-199. Compared with DBA/2J mice, D2.C-Tmevd2 mice developed a significantly less severe clinical disease course and EAE pathology in the spinal cord, confirming the existence of Eae3 and its linkage to Tmevd2 in this strain combination. Compared with DBA/2J and D2.C-Tmevd2, all three ISRC lines exhibited clinical disease courses of intermediate severity. Neither differences in ex vivo antigen-specific cytokine nor proliferative responses uniquely cosegregated with differences in disease severity. These results indicate that multiple quantitative trait loci (QTLs) within the Tmevd2/Eae3 interval influence EAE severity, one of which includes a homology region for a QTL found in MS by admixture mapping.


Assuntos
Animais Geneticamente Modificados/genética , Doenças Desmielinizantes/genética , Doenças Desmielinizantes/virologia , Encefalomielite Autoimune Experimental/genética , Predisposição Genética para Doença/genética , Locos de Características Quantitativas/genética , Animais , Animais Geneticamente Modificados/imunologia , Animais Geneticamente Modificados/virologia , Infecções por Cardiovirus/genética , Cromossomos de Mamíferos/genética , Doenças Desmielinizantes/imunologia , Modelos Animais de Doenças , Suscetibilidade a Doenças , Encefalomielite Autoimune Experimental/imunologia , Feminino , Marcadores Genéticos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Proteína Proteolipídica de Mielina/imunologia , Fragmentos de Peptídeos/imunologia , Theilovirus
2.
Cell Mol Biol (Noisy-le-grand) ; 49(2): 277-300, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12887108

RESUMO

The discoveries that activated macrophages produce 1alpha25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3), and that immune system cells express the vitamin D receptor (VDR), suggested that the vitamin D endocrine system influences immune system function. In this review, we compare and contrast how 1alpha,25-(OH)2D3 synthesis and degradation is regulated in kidney cells and activated macrophages, summarize data on hormone receptor function and expression in lymphocytes and myeloid lineage cells, and discuss how locally-produced 1alpha,25-(OH)2D3 may activate a negative feed-back loop at sites of inflammation. Studies of immunity in humans and animals lacking VDR function, or lacking vitamin D, are viewed to gain insight into the immunological functions of the vitamin D endocrine system. The strong associations between poor vitamin D nutrition, particular VDR alleles, and susceptibility to chronic mycobacterial infections, together with evidence that 1alpha,25-(OH)2D3 served as a vaccine adjuvant enhancing antibody-mediated immunity, suggest a model wherein high levels of 1alpha,25-(OH)2D3-liganded VDR transcriptional activity may promote the CD4+ T helper 2 (Th2) cell-mediated and mucosal antibody responses to cutaneous antigens in vivo. We also review a diverse and rapidly growing body of epidemiological, climatological, genetic, nutritional and biological evidence indicating that the vitamin D endocrine system functions in the establishment and/or maintenance of immunological self tolerance. Studies done in animal models of multiple sclerosis (MS), insulin-dependent diabetes mellitus (IDDM), inflammatory bowel disease (IBD), and transplantation support a model wherein the 1alpha,25-(OH)2D3 may augment the function of suppressor T cells that maintain self tolerance to organ-specific self antigens. The recent progress in infectious disease, autoimmunity and transplantation has stimulated a gratifying renaissance of interest in the vitamin D endocrine system and its role in immunological health.


Assuntos
Doenças Autoimunes/imunologia , Sistema Endócrino/imunologia , Vitamina D/imunologia , Doenças Transmissíveis/imunologia , Estrutura Terciária de Proteína , Receptores de Calcitriol/metabolismo , Vitamina D/metabolismo
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