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ER stress: an emerging regulator in GVHD development.
1Department of Microbiology & Immunology, Department of Medicine, and the Cancer Center, Medical College of Wisconsin, Milwaukee, WI, United States.
Frontiers in Immunology
|September 25, 2023
Summary
Allogeneic hematopoietic cell transplantation (HCT) can cause graft-versus-host disease (GVHD) due to endoplasmic reticulum (ER) stress. Targeting the unfolded protein response (UPR) may improve HCT effectiveness for hematologic malignancies.
Area of Science:
- Immunology
- Cellular Biology
- Oncology
Background:
- Allogeneic hematopoietic cell transplantation (allo-HCT) offers a potent therapy for hematologic malignancies.
- Graft-versus-host disease (GVHD) is a major complication limiting allo-HCT efficacy.
- Conditioning regimens induce endoplasmic reticulum (ER) stress in recipient cells, activating antigen-presenting cells (APCs) and donor cells.
Purpose of the Study:
- To review the role of ER stress and the unfolded protein response (UPR) in GVHD development.
- To explore therapeutic strategies targeting UPR for enhancing allo-HCT outcomes.
Main Methods:
- Literature review summarizing current research on ER stress, UPR, and GVHD.
- Analysis of the impact of UPR on immune cell function in the context of allo-HCT.
Main Results:
- ER stress and UPR are implicated in the pathogenesis of GVHD in both hematopoietic and non-hematopoietic cells.
- UPR influences the function of key immune cells, including T cells, B cells, macrophages, and dendritic cells (DCs).
Conclusions:
- Understanding the contribution of ER stress to GVHD is crucial for improving allo-HCT.
- Targeting the UPR pathway presents a promising therapeutic avenue to mitigate GVHD and enhance allo-HCT effectiveness in treating hematologic malignancies.
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