Faculty Collaboration Database

Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in Mice. Front Immunol 2021;12:749002

Date

11/12/2021

Pubmed ID

34759928

Pubmed Central ID

PMC8573259

DOI

10.3389/fimmu.2021.749002

Scopus ID

2-s2.0-85118722452 (requires institutional sign-in at Scopus site)   5 Citations

Abstract

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.

Author List

Pan P, Atkinson SN, Taylor B, Zhu H, Zhou D, Flejsierowicz P, Wang LS, Morse M, Liu C, Gunsolus IL, Chen X

Authors

Samantha N. Atkinson PhD Bioinformatics Analyst III in the Microbiology and Immunology department at Medical College of Wisconsin
Xiao Chen MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Caco-2 Cells
Feces
Gastrointestinal Microbiome
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Intestinal Mucosa
Lung
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Permeability
RNA, Ribosomal, 16S
Signal Transduction
Transplantation, Homologous
Vitamin A
Vitamins