The potential genes mediate the pathogenicity of allogeneic CD4+T cell in aGVHD mouse model

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). As a transcriptome sequencing technique, ribonucleic acid sequencing (RNA-Seq) is used to study alternative splicing and other forms of alternative isoform expression. Major histocompatibility complex (MHC)-matched and MHC-mismatched mouse bone marrow transplant (BMT) models were built to detect the difference of CD4+ lymphocyte in different tissues based on RNA-seq analysis. Four critical pathways were identified by enrichment analysis, including a lymphoid and a non-lymphoid cell, chemokine receptor binding chemokine, cytokine and cytokine receptor interaction pathway. At the same time, 11 novel hub genes that are most likely to participate in immunoregulatory and enriched pathways were identified, which were further validated by qRT-PCR. Besides, Cxcl7 was verified at the protein level. In summary, we revealed that DEGs and pathways related to immunoregulation played a vital role in the onset of aGVHD. These findings may provide some new clues for probing the pathogenesis and treatment of aGVHD.