Shift of graft-versus-host-disease target organ tropism by dietary vitamin A

• Published in: PloS one Vol. 7; no. 5; p. e38252
• Main Authors: Koenecke, Christian, Prinz, Immo, Bubke, Anja, Schreder, Alina, Lee, Chun-Wei, Pabst, Oliver, Förster, Reinhold
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.05.2012; Public Library of Science (PLoS)
• Subjects: Animal tissues; Animals; Biology; Bone marrow; CCR9 protein; CD4 antigen; Cell Count; Chemokines; Dendritic cells; Diet; Digestive system; Digestive tract; Fatalities; Foxp3 protein; Gastrointestinal tract; Gene expression; Gene Expression Regulation - immunology; Graft versus host disease; Graft vs Host Disease - immunology; Graft vs Host Disease - metabolism; Graft vs Host Disease - surgery; Graft-versus-host reaction; Gut-associated lymphoid tissues; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Homing; Homing receptors; House mouse; Immunology; Integrins; Integrins - metabolism; Interferon; Intestine; Intestines - immunology; Leukocyte migration; Ligands; Liver Diseases - immunology; Liver Diseases - metabolism; Liver transplants; Localization; Lymphatic system; Lymphocytes; Lymphocytes T; Lymphoid tissue; Medical schools; Medicine; Metabolites; Mice; Nutrient deficiency; Organs; Receptors; Receptors, CCR - metabolism; Retinoic acid; Rodents; Sexually transmitted diseases; Small intestine; Stem cell transplantation; Stem cells; Survival Analysis; T cell receptors; T cells; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Transplantation; Transplantation, Homologous - adverse effects; Transplants & implants; Tropism; Vitamin A; Vitamin A - metabolism; Vitamin A Deficiency - immunology; Vitamin A Deficiency - metabolism; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0038252

Gut-homing of donor T cells is causative for the development of intestinal GvHD in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Expression of the gut-specific homing receptors integrin-α4β7 and chemokine receptor CCR9 on T cells is imprinted in gut-associated lymphoid tissues (GALT) under the influence of the vitamin A metabolite retinoic acid. Here we addressed the role of vitamin A deficiency in HSCT-recipients for donor T cell migration in the course of experimental GvHD. Vitamin A-deficient (VAD) mice were prepared by feeding them a vitamin A-depleted diet. Experiments were performed in a C57BL/6 into BALB/c model of acute GvHD. We found that expression of integrin-α4β7 and CCR9 in GALT was reduced in VAD recipients after HSCT. Competitive in vivo homing assays showed that allogeneic T cells primed in VAD mice did not home as efficiently to the intestine as T cells primed in mice fed with standard diet (STD). The course of GvHD was ameliorated in VAD HSCT-recipients and, consequently, their survival was prolonged compared to recipients receiving STD. However, VAD-recipients were not protected and died of clinical GvHD. We found reduced numbers of donor T cells in the intestine but increased cell counts and tissue damage in other organs of VAD-recipients. Furthermore, we observed high IFN-γ(+)CD4(+) and low FoxP3(+)CD4(+) frequencies of total donor CD4(+) T cells in VAD as compared to STD recipients. Taken together, these results indicate that dietary vitamin A deficiency in HSCT-recipients changed target organ tropism in GvHD but also resulted in fatal inflammation after HSCT.