MHC-compatible bone marrow stromal/stem cells trigger fibrosis by activating host T cells in a scleroderma mouse model

Ogawa, Yoko; Morikawa, Satoru; Mabuchi, Yo; Suzuki, Sadafumi; Yaguchi, Tomonori; Sato, Yukio; Mukai, Sonoyo; Yaguchi, Shigeo; Inaba, Takaaki; Okamoto, Shinichiro; Kawakami, Yutaka; Tsubota, Kazuo; Matsuzaki, Yuji; Shimmura, Shigeto

doi:10.7554/elife.09394

Cited by 31 publications

(57 citation statements)

References 53 publications

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“…We chose this animal model because it is well recognized as an established model of cGVHD and because it reflects the inflammation and fibrosis in target organs of cGVHD [ 19 ]. We have published several studies on lacrimal gland cGVHD in humans [ 11 , 18 ] and mice [ 20 , 21 ] and have observed that the lacrimal gland pathology of this animal model is quite similar to that of humans [ 11 , 18 ]. Dry eye disease is a major problem for patients suffering from cGVHD after HSCT.…”

Section: Discussionmentioning

confidence: 99%

Reduced Expression of VAMP8 in Lacrimal Gland Affected by Chronic Graft-versus-Host Disease

Fukui

Ogawa

Mukai

et al. 2017

Journal of Ophthalmology

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Purpose To investigate whether the SNARE protein vesicle-associated membrane protein 8 (VAMP8) was implicated in the development of chronic ocular graft-versus-host disease (GVHD). Methods Firstly, the chronic GVHD (cGVHD) and Sjögren's syndrome (SS)-impaired lacrimal gland (LG) tissue sections from humans for diagnostic purpose were evaluated for VAMP8 expression by histopathology and immunohistochemistry. Next, serial changes of tear secretion and VAMP8 expression at both protein and mRNA level of LG in an animal cGVHD model compared with the syngeneic control. Results Decreased VAMP 8 expression in the cGVHD-affected human LG was detected in comparison with SS-affected LG. Tear secretion in the murine cGVHD model was significantly reduced compared with that in the syngeneic controls 8 weeks after BMT. Protein expression of VAMP8 in the cGVHD-affected LG in murine cGVHD was decreased in comparison with that in the controls. Gene expression of VAMP8 in the cGVHD-affected murine LG was significantly less than that in the syngeneic control 3 weeks after BMT. Conclusions Our results suggested that expression of VAMP8 in the cGVHD-affected LG was decreased and accordingly tear secretion in cGVHD was reduced. Collectively, the reduction of VAMP8 expression in the cGVHD-affected LG can be involved in the pathogenic processes of cGVHD-induced dry eye disease.

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Section: Discussionmentioning

confidence: 99%

Reduced Expression of VAMP8 in Lacrimal Gland Affected by Chronic Graft-versus-Host Disease

Fukui

Ogawa

Mukai

et al. 2017

Journal of Ophthalmology

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“…Murine models have shown that interaction between T cells and antigen-presenting cells, including macrophages contributed to the pathogenesis of ocular GVHD [17]. Migrating donor mesenchymal stem cells interact with T cells, leading to production of IL-6, a reduction of regulatory T cells, and an increase in Th17 effector T cells similar to what is seen in autoimmune pathologic processes [25].…”

Section: Preclinical Modelsmentioning

confidence: 99%

“…Several murine models of ocular GVHD have been studied previously [17,24,25]. In vitro analysis has shown that fibroblasts derived from GVHD-involved lacrimal glands have highly proliferative, invasive, and migratory characteristics [26].…”

Section: Preclinical Modelsmentioning

confidence: 99%

Ocular Graft-versus-Host Disease after Hematopoietic Cell Transplantation: Expert Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation

Inamoto¹,

Valdés-Sanz

Ogawa

et al. 2019

Biology of Blood and Marrow Transplantation

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A B S T R A C T Ocular graft-versus-host disease (GVHD) occurs in more than one-half of patients who develop chronic GVHD after allogeneic hematopoietic cell transplantation (HCT), causing prolonged morbidity that affects activities of daily living and quality of life. Here we provide an expert review of ocular GVHD in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Recent updates in ocular GVHD regarding pathophysiology, preclinical models, risk factors, prevention, screening, diagnosis, response criteria, evaluation measures, and treatment are discussed. Ocular GVHD involves at least 3 biological processes: lacrimal gland dysfunction, meibomian gland dysfunction, and corneoconjunctival inflammation. Preclinical models have identified several novel pathogenic mechanisms, including the renin angiotensin system and endoplasmic reticulum stress signaling, which can be targeted by therapeutic agents. Numerous studies have identified reliable tests for establishing diagnosis and response assessment of ocular GVHD. The efficacy of systemic and topical treatment for ocular GVHD is summarized. It is important that all health professionals caring for HCT recipients have adequate knowledge of ocular GVHD to provide optimal care.

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“…In particular, the following were noted: 1) the structures of intestinal villi in the inhibitor-treated small and large intestines were retained, in contrast to those in their vehicle-treated counterparts; 2) the vehicletreated skin was thicker, had less fatty tissue, and had greater density of collagen bundles than the inhibitortreated skin; and 3) meibomian glands in the vehiclemedicated eyes were fewer and smaller than their inhibitor-medicated equivalents. Furthermore, systemic fibrosis is highly problematic in GVHD (27,28). Mallory's staining indicated that fibrosis elicited by GVHD was considerably repressed in organs from inhibitor-medicated allo-BMT recipients in contrast to those from their vehicle-medicated equivalents (Fig.…”

Section: Immunohistochemical Investigation Into Inflammatory Cell Infmentioning

confidence: 99%

Inhibition of Vascular Adhesion Protein‐1 for Treatment of Graft‐Versus‐Host Disease in Mice

et al. 2018

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Graft-versus-host disease (GVHD) is a potentially lethal complication of hematopoietic stem cell transplantation (HSCT). GVHD comprises acute and chronic forms. To date, several approaches to treat acute GVHD or chronic GVHD have been reported. However, there is no literature precedent regarding all-in-one methods to address the 2 GVHD types. Severe inflammation in organs affected by GVHD is highly problematic, and vascular adhesion protein-1 (VAP-1) is known to be detrimentally involved in various inflammatory diseases. Based on the previous reports, we envisaged that there would be a link between GVHD and VAP-1, and we strived to create effective therapies for the 2 types of GVHD using a mouse model of GVHD. Our investigation indicated that expression of VAP-1 was elevated in organs disordered by GVHD. Hence, we subsequently attempted to block VAP-1 by using a novel inhibitor. Our results indicate that systemic injection of the inhibitor prevented aberrant influx of inflammatory cells into tissues and thereby mitigate GVHD-elicited inflammation and fibrosis. Collectively, our study suggests that the increased expression of VAP-1 is detrimentally associated with the development of GVHD and that the blockade of VAP-1 could be a promising medical modality to combat the acute and chronic variants.-Mukai, S., Ogawa, Y., Kawakami, Y., Mashima, Y., Tsubota, K. Inhibition of vascular adhesion protein-1 for treatment of graft-versus-host disease in mice.

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MHC-compatible bone marrow stromal/stem cells trigger fibrosis by activating host T cells in a scleroderma mouse model

Cited by 31 publications

References 53 publications

Reduced Expression of VAMP8 in Lacrimal Gland Affected by Chronic Graft-versus-Host Disease

Reduced Expression of VAMP8 in Lacrimal Gland Affected by Chronic Graft-versus-Host Disease

Inhibition of Vascular Adhesion Protein‐1 for Treatment of Graft‐Versus‐Host Disease in Mice

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