دورية أكاديمية
Endoplasmic Reticulum Stress Response Mediator IRE-1α Promotes Host Dendritic Cells in Graft-versus-Host Disease Development.
| العنوان: | Endoplasmic Reticulum Stress Response Mediator IRE-1α Promotes Host Dendritic Cells in Graft-versus-Host Disease Development. |
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| المؤلفون: | Choi HJ; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI.; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.; Cancer Center, Medical College of Wisconsin, Milwaukee, WI., Wu Y; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI.; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.; Cancer Center, Medical College of Wisconsin, Milwaukee, WI., McDaniel Mims B; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC., Pugel A; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI.; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.; Cancer Center, Medical College of Wisconsin, Milwaukee, WI., Tang CA; Center for Translational Research in Hematologic Malignancies, Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX., Tian L; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI.; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.; Cancer Center, Medical College of Wisconsin, Milwaukee, WI., Hu CA; Center for Translational Research in Hematologic Malignancies, Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX., Yu XZ; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI.; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.; Cancer Center, Medical College of Wisconsin, Milwaukee, WI. |
| المصدر: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2024 Aug 01; Vol. 213 (3), pp. 384-393. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Bethesda, MD : American Association of Immunologists Original Publication: Baltimore : Williams & Wilkins, c1950- |
| مواضيع طبية MeSH: | Dendritic Cells*/immunology , Graft vs Host Disease*/immunology , Endoplasmic Reticulum Stress*/immunology , Protein Serine-Threonine Kinases*/genetics , Protein Serine-Threonine Kinases*/metabolism , Endoribonucleases*/genetics , X-Box Binding Protein 1*/genetics , X-Box Binding Protein 1*/metabolism, Animals ; Mice ; Mice, Knockout ; Mice, Inbred C57BL ; Hematopoietic Stem Cell Transplantation ; Bone Marrow Transplantation ; Signal Transduction ; Cell Differentiation/immunology ; Graft vs Leukemia Effect/immunology |
| مستخلص: | Allogeneic hematopoietic cell transplantation is an effective treatment for hematologic malignancies, but the complications such as graft-versus-host disease (GVHD) can limit its benefit. The conditioning regimens before transplant, including chemotherapy or irradiation, can trigger endoplasmic reticulum stress. IRE-1α is a major endoplasmic reticulum stress mediator that can further activate both spliced XBP-1 (XBP-1s) and regulated IRE-1-dependent decay (RIDD). IRE-1α-XBP-1s signaling controls dendritic cell (DC) differentiation and Ag presentation, crucial in GVHD progression. In this study, we used DC-specific XBP-1-deficient mice as donors or recipients and observed that XBP-1s was crucial for host DCs in the induction of GVHD but dispensable for the graft-versus-leukemia response. To specifically target IRE-1α in the host, we treated recipient mice with the IRE-1α inhibitor B-I09 for 3 d prior to bone marrow transplantation, which significantly suppressed GVHD development while maintaining the graft-versus-leukemia effect. XBP-1-deficient or BI09-treated recipients showed reduced DC survival after irradiation and bone marrow transplantation. Inhibition of IRE-1α also led to a reduction in DC alloreactivity, subsequently decreasing the proliferation and activation of allogeneic T cells. With further study using RIDD-deficient DCs, we observed that RIDD was also required for optimal DC activation. Taken together, XBP-1s and RIDD both promote host DC survival and alloreactivity that contribute to GVHD development. (Copyright © 2024 by The American Association of Immunologists, Inc.) |
| معلومات مُعتمدة: | HL140953 HHS | National Institutes of Health (NIH); CA263140 HHS | National Institutes of Health (NIH); CA163910 HHS | National Institutes of Health (NIH); CA248354 HHS | National Institutes of Health (NIH) |
| المشرفين على المادة: | EC 2.7.11.1 (Protein Serine-Threonine Kinases) EC 3.1.- (Endoribonucleases) 0 (X-Box Binding Protein 1) EC 2.7.11.1 (Ern1 protein, mouse) 0 (Xbp1 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20240612 Date Completed: 20240715 Latest Revision: 20240716 |
| رمز التحديث: | 20240717 |
| DOI: | 10.4049/jimmunol.2300616 |
| PMID: | 38864663 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1550-6606 |
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| DOI: | 10.4049/jimmunol.2300616 |