Purpose: This study aimed to clarify the mechanisms and assess the characteristics of the chronic graft-versus-host disease (cGVHD) fibrosis in the lacrimal gland (LG) of mice.
Methods: Histopathology of LG tissues was examined by immunohistochemistry and electron microscopy. Cultured fibroblasts derived from the LG were analyzed by phase-contrast microscopy, immunocytochemistry, flow cytometry, proliferation assay, and invasion and migration assays.
Results: Cultured murine LG fibroblasts in cGVHD were spindle-shaped and relatively small, whereas those from syngeneic controls were polygon-shaped and relatively large. Flow cytometric analysis showed that the LG fibroblasts in cGVHD had elevated HSP47 levels. The LG fibroblasts in cGVHD also showed increased expression of major histocompatibility complex class II. Furthermore, the proportion of Sca-1PDGFR-α cells among the LG fibroblasts in cGVHD was considerably increased compared with controls. Cell counting kit-8 assays demonstrated that the LG fibroblasts in cGVHD were highly proliferative, and cell invasion assays indicated that they were highly invasive with high migration ability.
Conclusions: LG fibroblasts in cGVHD can be aberrantly activated, thereby eliciting fibrosis by producing excessive extracellular matrix, leading to LG dysfunction in mice.
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http://dx.doi.org/10.1097/ICO.0000000000001411 | DOI Listing |
EBioMedicine
December 2024
Department of Hematology and Cell Therapy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang province, PR China. Electronic address:
Background: Bronchiolitis obliterans syndrome (BOS) is one of the most devastating outcomes of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This remains an area of unmet clinical need for optimal therapy for BOS patients partly due to the limited understanding of pathogenic mechanisms.
Methods: We collected blood samples from 22 patients with cGVHD and 11 patients without cGVHD following allo-HSCT.
Ocul Surf
October 2024
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
Purpose: The topical administration of spironolactone, a mineralocorticoid receptor antagonist (MRA) improves dry eye symptoms in patients with ocular graft-versus-host disease (GVHD); however, the detailed mechanism remains unclear. This study aimed to investigate the effects of spironolactone eyedrops on the ocular surface using a chronic GVHD (cGVHD) mouse model and to determine the expression of the mineralocorticoid receptor (MR).
Methods: A cGVHD mouse model was established by allogeneic bone marrow transplantation (BMT) from B10.
Rinsho Ketsueki
June 2024
Department of Internal Medicine III, Division of Hematology and Cell Therapy, Yamagata University Faculty of Medicine.
Chronic graft-versus-host disease (cGVHD) negatively impacts long-term survival and quality of life (QOL) after allogeneic hematopoietic cell transplantation. Corticosteroids are the first-line treatment for cGVHD, but approximately 30% to 70% of patients develop steroid-refractory cGVHD (SR-cGVHD), which has an extremely poor prognosis. The pathophysiology of cGVHD is more complicated than acute GVHD, but recent advances using murine models in conjunction with human studies indicate three major phases: 1) acute inflammation, 2) chronic inflammation with loss of immune tolerance, and 3) disrupted target organ homeostasis and fibrosis.
View Article and Find Full Text PDFArthritis Res Ther
May 2024
Department of Dermatology, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, 910-1193, Japan.
Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular injury and inflammation, followed by excessive fibrosis of the skin and other internal organs, including the lungs. CX3CL1 (fractalkine), a chemokine expressed on endothelial cells, supports the migration of macrophages and T cells that express its specific receptor CX3CR1 into targeted tissues. We previously reported that anti-CX3CL1 monoclonal antibody (mAb) treatment significantly inhibited transforming growth factor (TGF)-β1-induced expression of type I collagen and fibronectin 1 in human dermal fibroblasts.
View Article and Find Full Text PDFAnn Rheum Dis
August 2024
Department of Rheumatology, University Hospital of Düsseldorf, Düsseldorf, Nordrhein-Westfalen, Germany.
Background: The interleukin (IL)-1 receptor accessory protein (IL1RAP) is an essential coreceptor required for signalling through the IL-1, IL-33 and IL-36 receptors. Here, we investigate the antifibrotic potential of the combined inhibition of these cytokines by an anti-IL1RAP antibody to provide a scientific background for clinical development in systemic sclerosis (SSc).
Methods: The expression of IL1RAP-associated signalling molecules was determined by data mining of publicly available RNA sequencing (RNAseq) data as well as by imaging mass cytometry.
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