title: Disease severity and mortality can be independently regulated in a mouse model of experimental graft versus host disease.
abstract: Graft versus host disease (GVHD) is the major limitation of allogeneic hematopoietic stem cell transplantation (HSCT) presenting high mortality and morbidity rates. However, the exact cause of death is not completely understood and does not correlate with specific clinical and histological parameters of disease. Here we show, by using a semi-allogeneic mouse model of GVHD, that mortality and morbidity can be experimentally separated. We injected bone marrow-derived dendritic cells (BMDC) from NOD2/CARD15-deficient donors into semi-allogeneic irradiated chimaeras and observed that recipients were protected from death. However, no protection was observed regarding clinical or pathological scores up to 20 days after transplantation. Protection from death was associated with decreased bacterial translocation, faster hematologic recovery and epithelial integrity maintenance despite mononuclear infiltration at day 20 post-GVHD induction with no skew towards different T helper phenotypes. The protected mice recovered from aGVHD and progressively reached scores compatible with healthy animals. Altogether, our data indicate that severity and mortality can be separate events providing a model to study transplant-related mortality.
authors: Divisão de Medicina Experimental, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil; Departamento de Imunologia, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Rômulo G
authors: RG
authors: Galvani
authors: Divisão de Medicina Experimental, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil; Departamento de Imunologia, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Ramon
authors: R
authors: Lemos
authors: Divisão de Medicina Experimental, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors: Rômulo B
authors: RB
authors: Areal
authors: Divisão de Medicina Experimental, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors: Pollyanna A
authors: PA
authors: Salvador
authors: Departamento de Biologia Celular, Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors: Dario S
authors: DS
authors: Zamboni
authors: Divisão de Medicina Experimental, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil; NUPEM, Campus Macaé Professor Aloísio Teixeira, Universidade Federal do Rio de Janeiro, Macaé, Rio de Janeiro, Brazil.
authors: João Luiz M
authors: JL
authors: Wanderley
authors: Divisão de Medicina Experimental, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil; Departamento de Imunologia, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Laboratorio de Pesquisa sobre o Timo, Instituo Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
authors: Adriana
authors: A
authors: Bonomo
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D055786:Gene Knockout Techniques; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality*; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000172:deficiency / Q000235:genetics; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014184:Transplantation, Homologous / Q000009:adverse effects
chemical_list: D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse
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