Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in Mice
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 G...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.749002/full |
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| author | Pan Pan Pan Pan Samantha N. Atkinson Samantha N. Atkinson Brian Taylor Brian Taylor Haojie Zhu Haojie Zhu Dian Zhou Dian Zhou Philip Flejsierowicz Philip Flejsierowicz Li-Shu Wang Li-Shu Wang Matthew Morse Matthew Morse Chen Liu Ian L. Gunsolus Xiao Chen Xiao Chen |
| author_facet | Pan Pan Pan Pan Samantha N. Atkinson Samantha N. Atkinson Brian Taylor Brian Taylor Haojie Zhu Haojie Zhu Dian Zhou Dian Zhou Philip Flejsierowicz Philip Flejsierowicz Li-Shu Wang Li-Shu Wang Matthew Morse Matthew Morse Chen Liu Ian L. Gunsolus Xiao Chen Xiao Chen |
| author_sort | Pan Pan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T19:20:45Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T19:20:45Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-62455d10f0a041d4be29f0fccd0e797c2022-12-21T17:34:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-10-011210.3389/fimmu.2021.749002749002Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in MicePan Pan0Pan Pan1Samantha N. Atkinson2Samantha N. Atkinson3Brian Taylor4Brian Taylor5Haojie Zhu6Haojie Zhu7Dian Zhou8Dian Zhou9Philip Flejsierowicz10Philip Flejsierowicz11Li-Shu Wang12Li-Shu Wang13Matthew Morse14Matthew Morse15Chen Liu16Ian L. Gunsolus17Xiao Chen18Xiao Chen19Division of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Medicine, Medical College of Wisconsin, Milwaukee, WI, United StatesCenter for Microbiome Research, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, United StatesDivision of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Medicine, Medical College of Wisconsin, Milwaukee, WI, United StatesDivision of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Medicine, Medical College of Wisconsin, Milwaukee, WI, United StatesDivision of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Medicine, Medical College of Wisconsin, Milwaukee, WI, United StatesDivision of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Medicine, Medical College of Wisconsin, Milwaukee, WI, United StatesDivision of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Medicine, Medical College of Wisconsin, Milwaukee, WI, United StatesDivision of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Medicine, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Pathology, Yale University School of Medicine, New Haven, CT, United StatesDepartment of Pathology, Medical College of Wisconsin, Milwaukee, WI, United StatesDivision of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Medicine, Medical College of Wisconsin, Milwaukee, WI, United StatesGraft-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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.749002/fullretinoic acidintestinal barriergut microbiotavitamin Agraft-versus-host disease |
| spellingShingle | Pan Pan Pan Pan Samantha N. Atkinson Samantha N. Atkinson Brian Taylor Brian Taylor Haojie Zhu Haojie Zhu Dian Zhou Dian Zhou Philip Flejsierowicz Philip Flejsierowicz Li-Shu Wang Li-Shu Wang Matthew Morse Matthew Morse Chen Liu Ian L. Gunsolus Xiao Chen Xiao Chen Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in Mice Frontiers in Immunology retinoic acid intestinal barrier gut microbiota vitamin A graft-versus-host disease |
| title | Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in Mice |
| title_full | Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in Mice |
| title_fullStr | Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in Mice |
| title_full_unstemmed | Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in Mice |
| title_short | Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in Mice |
| title_sort | retinoic acid signaling modulates recipient gut barrier integrity and microbiota after allogeneic hematopoietic stem cell transplantation in mice |
| topic | retinoic acid intestinal barrier gut microbiota vitamin A graft-versus-host disease |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.749002/full |
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