The retinoic acid-metabolizing enzyme Cyp26b1 regulates CD4 T cell differentiation and function

Alistair Chenery, Kyle Burrows, Frann Antignano, T. Michael Underhill, Martin Petkovich, Colby Zaph

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16 Citations (Scopus)


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.
Original languageEnglish
Article numbere72308
Number of pages8
JournalPLoS ONE
Issue number8
Publication statusPublished - 22 Aug 2013
Externally publishedYes

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