Abstract
Acute graft-versus-host disease (aGVHD) remains a significant and severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Due to the occurrence of aGVHD, allo-HSCT significantly increases the mortality rate compared with autologous hematopoietic stem cell transplantation (auto-HSCT). In this study, auto-HSCT and allo-HSCT aGVHD mouse models were built to detect the difference in CD4+ lymphocyte in different tissues based on ribonucleic acid sequencing (RNA-Seq) analysis. Clustering analysis, functional annotation, and pathway enrichment analysis were performed on differentially expressed genes (DEGs). The protein-protein interaction (PPI) network was used to find hub genes. CD4+T cells were activated by MLR and cytokine stimulation. Cells were sorted out by a flow cell sorter. The selected genes were verified by qRT-PCR, histology, and immunofluorescence staining. The GSE126518 GEO dataset was used to verify the hub genes. Enrichment analysis revealed four immune-related pathways that play an important role in aGVHD, including immunoregulatory interactions between a lymphoid and a nonlymphoid cell, chemokine receptors binding chemokines, cytokine and cytokine receptor interaction, and the chemokine signaling pathway. At the same time, with the PPI network, 11 novel hub genes that were most likely to participate in immunoregulation in aGVHD were identified, which were further validated by qRT-PCR and the GSE126518 dataset. Besides, the protein expression level of Cxcl7 was consistent with the sequencing results. In summary, this study revealed that immunoregulation-related DEGs and pathways played a vital role in the onset of aGVHD. These findings may provide some new clues for probing the pathogenesis and treatment of aGVHD.
Highlights
Allogeneic hematopoietic stem cell transplantation is an effective treatment for various haematological diseases wherein blood cells are unavailable in unmodified autologous transplants
Unblocking of NMDA receptor...| reactome Cell surface interactions at the ... | reactome Scavenging of heme from plasma | reactome O2/CO2 exchange in erthrocytes | reactome Erthrocytes take up carbon dioxide ... | reactome Chemokine receptors bind chemokines | reactome Erthrocytes take up oxygen and ... | reactome Peptide ligand-binding receptors | reactome Immunoregulatory interactions... | reactome
To further explore the immunopathological mechanism of GVHD, we focused on differentially expressed genes (DEGs) of the spleen, liver, and lung hub genes with immunoregulatory functions in a murine model of allogeneic HSCT compared with splenic CD4+T cells from mice with autologous transplantation
Summary
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is an effective treatment for various haematological diseases wherein blood cells are unavailable in unmodified autologous transplants. The occurrence of aGVHD can be divided into three stages according to its sequence Preconditioning regimens such as radiotherapy and chemotherapy as well as infection cause epithelial cell damage and an inflammatory environment, while the expression of the MHC antigen in the recipient initiates the recognition of donor T cells. The interactions between T cell receptors, antigen major histocompatibility complexes (anti-MHC), costimulatory molecules, and cytokines activate the donor T cells at an early stage. We found a phenomenon that the infiltration of activated effector CD4+T cells in these tissues was different in the aGVHD mouse model in this study. In this study, using RNA-Seq, we first analyzed the gene expressing profiles of CD4+T cells from the spleen, lung, and liver tissues sampled in auto-HSCT and allo-HSCT recipient mice and identified the differentially expressed genes (DEGs) to characterize CD4+T cells in aGVHD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
