Vitamin A to reduce gut leak and GVHD?

Carpenter, Paul A.

doi:10.1182/blood-2017-03-773226

Cited by 5 publications

(6 citation statements)

References 10 publications

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“…The discrepancy between the two studies may originate from differences in study populations (pediatric vs. adult patients) and the timing of vitamin A measurement (post-transplant vs. pretransplant). In addition, there is an interest in using vitamin A supplementation to reduce GVHD risk in the clinic (48). Therefore, it is imperative to test the applicability of this strategy in animal models of GVHD.…”

Section: Discussionmentioning

confidence: 99%

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Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in Mice

et al. 2021

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Graft-versus-host disease (GVHD) remains a major complication after allogeneic hematopoietic stem cell transplantation (HSCT). An impaired intestinal epithelial barrier is an important component of GVHD pathogenesis. However, contributing host factors that modulate mucosal barrier integrity during GVHD are poorly defined. We hypothesized that vitamin A and retinoic acid (RA) exert positive impacts on maintaining intestinal barrier function after HSCT, thus preventing or dampening GVHD severity. Unexpectedly, we found that exogenous RA increased intestinal permeability of recipient mice after allogeneic HSCT. Serum bacterial endotoxin levels were significantly higher in GVHD mice fed a vitamin A-high (VAH) diet compared to those fed a vitamin A-normal (VAN) diet, indicating a more compromised intestinal barrier function. Furthermore, VAH mice showed more severe lung GVHD with increased donor T cell infiltration in this tissue and died significantly faster than VAN recipients. 16S rRNA sequencing of fecal samples revealed significant differences in the diversity and composition of gut microbiota between VAN and VAH transplant recipients. Collectively, we show that retinoic acid signaling may negatively impact intestinal barrier function during GVHD. Mild vitamin A supplementation is associated with increased lung GVHD and more profound gut dysbiosis. Micronutrients such as vitamin A could modulate complications of allogeneic HSCT, which may be mediated by shaping gut microbiota.

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Section: Discussionmentioning

confidence: 99%

“…pre-transplant). In addition, there is an interest in using vitamin A supplementation to reduce GVHD risk in the clinic ( 48 ). Therefore, it is imperative to test the applicability of this strategy in animal models of GVHD.…”

Section: Discussionmentioning

confidence: 99%

Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in Mice

et al. 2021

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“…We therefore focused on the lesswell-defined mechanisms by which barrier loss promotes ongoing attack of recipient tissues, i.e., GVHD propagation, which is associated with local T cell recruitment and apoptosis of intestinal crypt epithelial cells (5,6). Identification of these mech-anisms and means to prevent GVHD propagation could have tremendous therapeutic potential (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

“…Sustained intestinal barrier loss has been proposed as a contributor to GVHD propagation based on the observation that the degree of intestinal barrier loss correlates with disease severity in patients and mice with GVHD (4,6,(8)(9)(10)(11)(12)(13). However, it remains unclear whether this increased permeability is a consequence of disease or a primary driver of disease propagation.…”

Section: Introductionmentioning

confidence: 99%

Graft-versus-host disease propagation depends on increased intestinal epithelial tight junction permeability

Nalle¹,

Zuo²,

Ong³

et al. 2019

Journal of Clinical Investigation

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Graft-versus-host disease (GVHD) is a complication of hematopoietic stem cell transplantation (HSCT) that affects multiple organs. GVHD-associated intestinal damage can be separated into two distinct phases, initiation and propagation, which correspond to conditioning-induced damage and effector T cell activation and infiltration, respectively. Substantial evidence indicates that intestinal damage induced by pretransplant conditioning is a key driver of GVHD initiation. Here, we aimed to determine the impact of dysregulated intestinal permeability on the subsequent GVHD propagation phase. The initiation phase of GVHD was unchanged in mice lacking long MLCK (MLCK210), an established regulator of epithelial tight junction permeability. However, MLCK210-deficient mice were protected from sustained barrier loss and exhibited limited GVHD propagation, as indicated by reduced histopathology, fewer CD8 + effector T cells in the gut, and improved overall survival. Consistent with these findings, intestinal epithelial MLCK210 expression and enzymatic activity were similarly increased in human and mouse GVHD biopsies. Intestinal epithelial barrier loss mediated by MLCK210 is therefore a key driver of the GVHD propagation. These data suggest that inhibition of MLCK210-dependent barrier regulation may be an effective approach to limiting GVHD progression.

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“…Their levels may also have prognostic value, serving as independent risk factors for predicting the severity of organ-specific or systemic GVHD. Most importantly, nutritional intervention before and after allogeneic HSCT may be used as an adjuvant therapy to reduce GVHD risk and improve the outcome of allogeneic HSCT (95, 97, 98). We propose that GVHD research using animal models should consider dietary composition.…”

Section: Effects Of Vitamin D On Gvhdmentioning

confidence: 99%

The Role of Micronutrients in Graft-VS.-Host Disease: Immunomodulatory Effects of Vitamins A and D

Chen

Mayne

2018

Front. Immunol.

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Graft-vs.-host disease (GVHD) remains a major obstacle to the success of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD occurs because donor T cells in the allograft recognize the genetically disparate host as foreign and attack the transplant recipient's tissues. While genetic incompatibility between donor and recipient is the primary determinant for the extent of alloimmune response, GVHD incidence and severity are also influenced by non-genetic factors. Recent advances in immunology establish that environmental factors, including dietary micronutrients, contribute significantly to modulating various immune responses and may influence the susceptibility to autoimmune and inflammatory diseases of experimental animals and humans. Emerging clinical and preclinical evidence indicates that certain micronutrients may participate in regulating GVHD risk after allogeneic HSCT. In this review, we summarize recent advances in our understanding with respect to the potential role of micronutrients in the pathogenesis of acute and chronic GVHD, focusing on vitamins A and D.

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Vitamin A to reduce gut leak and GVHD?

Cited by 5 publications

References 10 publications

Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in Mice

Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in Mice

Graft-versus-host disease propagation depends on increased intestinal epithelial tight junction permeability

The Role of Micronutrients in Graft-VS.-Host Disease: Immunomodulatory Effects of Vitamins A and D

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