title: The retinoic acid-metabolizing enzyme Cyp26b1 regulates CD4 T cell differentiation and function.
abstract: The vitamin A metabolite retinoic acid (RA) has potent immunomodulatory properties that affect T cell differentiation, migration and function. However, the precise role of RA metabolism in T cells remains unclear. Catabolism of RA is mediated by the Cyp26 family of cytochrome P450 oxidases. We examined the role of Cyp26b1, the T cell-specific family member, in CD4(+) T cells. Mice with a conditional knockout of Cyp26b1 in T cells (Cyp26b1 (-/-) mice) displayed normal lymphoid development but showed an increased sensitivity to serum retinoids, which led to increased differentiation under both inducible regulatory T (iTreg) cell- and TH17 cell-polarizing conditions in vitro. Further, Cyp26b1 expression was differentially regulated in iTreg and TH17 cells. Transfer of naïve Cyp26b1 (-/-) CD4(+) T cells into Rag1 (-/-) mice resulted in significantly reduced disease in a model of T cell-dependent colitis. Our results show that T cell-specific expression of Cyp26b1 is required for the development of T cell-mediated colitis and may be applicable to the development of therapeutics that target Cyp26b1 for the treatment of inflammatory bowel disease.
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Alistair
authors.initials: A
authors.lastname: Chenery
authors.forename: Kyle
authors.initials: K
authors.lastname: Burrows
authors.forename: Frann
authors.initials: F
authors.lastname: Antignano
authors.forename: T Michael
authors.initials: TM
authors.lastname: Underhill
authors.forename: Martin
authors.initials: M
authors.lastname: Petkovich
authors.forename: Colby
authors.initials: C
authors.lastname: Zaph
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation; D003092:Colitis / Q000276:immunology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D000072516:Retinoic Acid 4-Hydroxylase
chemical_list: D003577:Cytochrome P-450 Enzyme System; C000607081:Cyp26b1 protein, mouse; D000072516:Retinoic Acid 4-Hydroxylase