The therapeutic potential of hematopoietic cell transplantation (HCT) for the treatment of malignant disease relies on graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) responses to eradicate residual tumor cells via immunological mechanisms. Graft-versus-host disease (GVHD) is still a major cause of transplant-related morbidity and mortality following allogeneic HCT (allo-HCT). GVHD is clinically described in two forms: acute (aGVHD) and chronic (cGVHD). aGVHD is primarily induced by T cells commonly characterized by a type I T-cell response; whereas cGVHD is induced by both T and B cells, similar in nature to that of autoimmune disorders. Despite advances in patient care and pharmacological prophylaxis strategies, the incidence of GVHD, particularly cGVHD, has not significantly reduced over the years. In fact, beyond steroid-based therapy, effective treatment options are very limited. Therefore, we are in urgent need of further understanding GVHD pathogenesis and identifying novel therapeutic targets for the prevention and treatment of this devastating disease as a major complication of allo-HCT.
Since allo-reactive donor T cells are central to aGVHD pathophysiology, research has been focused on donor T-cell (i) activation; (ii) co-stimulatory/co-inhibitory signals; (iii) differentiation, (iv) migration, and (v) antigen-experience stages. The regulation of T cell allo-responses by protein kinases, metabolites, non-coding RNAs and other post-transcriptional mechanisms has also gained substantial attention in recent years. Beyond donor T cells, other lymphoid cells including NK, NKT and innate lymphoid cells (ILCs) also contribute to aGVHD pathogenesis. In addition, microbiota, tissue injury/repair and thymopoiesis are also critically involved in aGVHD pathogenesis.
The pathophysiology of cGVHD is characterized by fibrosis with inflammation resulting in organ dysfunction. Immunological characteristics of cGVHD include (i) aberrant conventional T and B cell activation, differentiation and interactions; and (ii) decreased production and development of regulatory T cells (Tregs). Research on cGVHD is now progressing towards understanding the roles of B-cell signaling, activation, germinal center formation and plasma cell differentiation; as well as the roles of T-cell signaling, activation and differentiation into T helper subsets and iTregs in this disease.
In this Research Topic, we welcome the submission of Original Research and state-of-the-art Review and Mini-Review articles on the pathogenesis and therapy of GVHD which cover, but are not limited to, the following sub-topics:
1. The role of co-stimulatory/co-inhibitor signals in GVHD.
2. T-cell activation and differentiation in GVHD.
3. Alterations in T-cell and B-cell metabolism under allo-HCT conditions.
4. B-cell signaling, activation, and differentiation in GVHD.
5. Lymphocyte migration and tissue distribution in GVHD conditions.
6. Post-transcriptional regulation of T cells or B cells under GVHD conditions.
7. The role of the microbiota and metabolites in the pathogenesis of GVHD.
8. Tissue injury and repair following allo-HCT.
9. The role of other lymphoid cell subsets, e.g. NK and ILCs, in GVHD.
10. Potential therapeutic targets for treating aGVHD and/or cGVHD.
The therapeutic potential of hematopoietic cell transplantation (HCT) for the treatment of malignant disease relies on graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) responses to eradicate residual tumor cells via immunological mechanisms. Graft-versus-host disease (GVHD) is still a major cause of transplant-related morbidity and mortality following allogeneic HCT (allo-HCT). GVHD is clinically described in two forms: acute (aGVHD) and chronic (cGVHD). aGVHD is primarily induced by T cells commonly characterized by a type I T-cell response; whereas cGVHD is induced by both T and B cells, similar in nature to that of autoimmune disorders. Despite advances in patient care and pharmacological prophylaxis strategies, the incidence of GVHD, particularly cGVHD, has not significantly reduced over the years. In fact, beyond steroid-based therapy, effective treatment options are very limited. Therefore, we are in urgent need of further understanding GVHD pathogenesis and identifying novel therapeutic targets for the prevention and treatment of this devastating disease as a major complication of allo-HCT.
Since allo-reactive donor T cells are central to aGVHD pathophysiology, research has been focused on donor T-cell (i) activation; (ii) co-stimulatory/co-inhibitory signals; (iii) differentiation, (iv) migration, and (v) antigen-experience stages. The regulation of T cell allo-responses by protein kinases, metabolites, non-coding RNAs and other post-transcriptional mechanisms has also gained substantial attention in recent years. Beyond donor T cells, other lymphoid cells including NK, NKT and innate lymphoid cells (ILCs) also contribute to aGVHD pathogenesis. In addition, microbiota, tissue injury/repair and thymopoiesis are also critically involved in aGVHD pathogenesis.
The pathophysiology of cGVHD is characterized by fibrosis with inflammation resulting in organ dysfunction. Immunological characteristics of cGVHD include (i) aberrant conventional T and B cell activation, differentiation and interactions; and (ii) decreased production and development of regulatory T cells (Tregs). Research on cGVHD is now progressing towards understanding the roles of B-cell signaling, activation, germinal center formation and plasma cell differentiation; as well as the roles of T-cell signaling, activation and differentiation into T helper subsets and iTregs in this disease.
In this Research Topic, we welcome the submission of Original Research and state-of-the-art Review and Mini-Review articles on the pathogenesis and therapy of GVHD which cover, but are not limited to, the following sub-topics:
1. The role of co-stimulatory/co-inhibitor signals in GVHD.
2. T-cell activation and differentiation in GVHD.
3. Alterations in T-cell and B-cell metabolism under allo-HCT conditions.
4. B-cell signaling, activation, and differentiation in GVHD.
5. Lymphocyte migration and tissue distribution in GVHD conditions.
6. Post-transcriptional regulation of T cells or B cells under GVHD conditions.
7. The role of the microbiota and metabolites in the pathogenesis of GVHD.
8. Tissue injury and repair following allo-HCT.
9. The role of other lymphoid cell subsets, e.g. NK and ILCs, in GVHD.
10. Potential therapeutic targets for treating aGVHD and/or cGVHD.
