RESUMO
Immune cells are generated from hematopoietic stem cells (HSCs) in the bone marrow (BM). Immune stimulation can rapidly activate HSCs out of their quiescent state to accelerate the generation of immune cells. HSCs' activation follows various viral or bacterial stimuli, and we sought to investigate the hypersensitivity immune response. Surprisingly, the Ova-induced hypersensitivity peritonitis model finds no significant changes in BM HSCs. HSC markers cKIT, SCA1, CD48, CD150, and the Fgd5-mCherry reporter showed no significant difference from control. Functionally, hypersensitivity did not alter HSCs' potency, as assayed by transplantation. We further characterized the possible impact of hypersensitivity using RNA-sequencing of HSCs, finding minor changes at the transcriptome level. Moreover, hypersensitivity induced no significant change in the proliferative state of HSCs. Therefore, this study suggests that, in contrast to other immune stimuli, hypersensitivity has no impact on HSCs.
Assuntos
Imunidade Adaptativa/imunologia , Células da Medula Óssea/imunologia , Células-Tronco Hematopoéticas/imunologia , Hipersensibilidade/imunologia , Transcriptoma/imunologia , Animais , Ataxina-1/genética , Ataxina-1/imunologia , Ataxina-1/metabolismo , Células da Medula Óssea/metabolismo , Antígeno CD48/genética , Antígeno CD48/imunologia , Antígeno CD48/metabolismo , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/metabolismo , Camundongos Congênicos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/imunologia , Proteínas Proto-Oncogênicas c-kit/metabolismo , RNA-Seq/métodos , Transcriptoma/genéticaRESUMO
Mesenchymal stromal cells (MSCs) have therapeutic potential for the prevention and treatment of graft-versus-host disease (GVHD). However, MSCs comprise several subpopulations, which have not been individually assessed for their role in GVHD suppression. In this study, we assessed the immunosuppressive effect of bone-related Sca1(+) MSCs on acute GVHD in a MHC-mismatched mouse model of allogeneic hematopoietic stem cell transplantation (HCT). Our results showed that Sca1(+) MSCs decreased the severity of acute GVHD (aGVHD) and prolonged the survival period of allogeneic HCT recipients. This effect was exerted through lowered T lymphocyte infiltration in target organs and by inhibition of CD80/86 expression on host dendritic cells. Furthermore, the expression of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a negative regulator of T cells, was elevated in the recipient splenocytes. In conclusion, bone-related Sca1(+) MSCs subpopulation suppressed GVHD and could be a novel treatment for acute GVHD.