Doença do Enxerto Contra o Hospedeiro (DECH) induz resposta inflamatória na medula espinhal e Gânglios da Raiz Dorsal (DRG)

Abstract

Graft-versus-host disease (GVHD) is a systemic inflammatory disorder that occurs after allogeneic hematopoietic cell transplantation when donor immune cells recognize host antigenic disparities. These disparities involve major histocompatibility antigens (HLA) and minor histocompatibility antigens (miHag). Lower compatibility between donor and recipient increases the risk of GVHD. While organs such as the intestine, liver, spleen, and skin are well-studied targets, others like the lung, thymus, kidney, and nervous system have gained attention. In this study, we investigated the cellular and molecular profile in the spinal cord and dorsal root ganglia (DRG) of mice with GVHD.C57BL/6 mice underwent lethal irradiation (9Gy) followed by intravenous infusion of splenocytes and bone marrow cells from BALB/c donor mice. GVHD progression was monitored, revealing a continuous worsening of clinical signs in affected animals, whereas the control group remained stable. Mortality in the GVHD group began on day 16 and reached 100% by day 36, while the control group showed 100% survival.Molecular analysis showed a significant increase in IL-1β and TNF-α mRNA expression in the spinal cord and IL-1β, CCL2, and IFN-γ in the DRG of GVHD mice. Furthermore, immunofluorescence revealed leukocyte accumulation in the DRGs. Using a humanized GVHD (GVHDhu) model, with peripheral blood mononuclear cells (PBMCs) transplanted into NSG mice, we observed the accumulation of human CD45+ cells in DRGs and meninges.To evaluate the functional impact of the inflammatory response, behavioral parameters were analyzed. GVHD mice traveled shorter distances and spent less time standing on two legs compared to controls, indicating functional impairment associated with nervous system inflammation.These findings demonstrate, for the first time, that GVHD induces an inflammatory response in the spinal cord and DRGs, establishing these organs as potential targets of the disease.