Inhibiting retinoic acid signaling ameliorates graft-versus-host disease by modifying T-cell differentiation and intestinal migration

Author:

Aoyama Kazutoshi1,Saha Asim1,Tolar Jakub1,Riddle Megan J.1,Veenstra Rachelle G.1,Taylor Patricia A.1,Blomhoff Rune2,Panoskaltsis-Mortari Angela1,Klebanoff Christopher A.3,Socié Gérard4,Munn David H.5,Murphy William J.6,Serody Jonathan S.7,Fulton LeShara M.7,Teshima Takanori8,Chandraratna Roshantha A.9,Dmitrovsky Ethan10,Guo Yanxia11,Noelle Randolph J.11,Blazar Bruce R.1

Affiliation:

1. University of Minnesota Cancer Center and Department of Pediatrics, Division of Blood and Marrow Transplantation, Minneapolis, MN;

2. Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway;

3. Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD;

4. Service d'Hématologie-Greffe, Hôpital Saint-Louis, Assistance Publique-Hopitaux de Paris, Université Paris VII Denis-Diderot, and Unité Institut National de la Santé et de la Recherche Médicale U940, Paris, France;

5. Department of Pediatrics, Medical College of Georgia, Augusta, GA, and Immunotherapy Center, Medical College of Georgia, Augusta, GA;

6. Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA;

7. Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC;

8. Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;

9. Drug Discovery and Development, IO Therapeutics Inc., Santa Ana, CA; and

10. Department of Pharmacology and Toxicology and the

11. Department of Microbiology and Immunology at the Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Lebanon, NH

Abstract

Key Points Expression and function of vitamin A metabolizing enzymes are increased in the intestine and mesenteric lymph nodes during GVHD. Inhibiting donor T-cell RAR signaling reduces Th1 differentiation, gut homing, and GVHD while preserving graft-versus-lymphoma effects.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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