Journal
PLOS ONE
Volume 8, Issue 8, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0072308
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Funding
- Canadian Institutes of Health Research [MSH-95368, MOP-89773, MOP-106623]
- Canada Foundation for Innovation grant
- CIHR/Canadian Association of Gastroenterology/Crohn's and Colitis Foundation of Canada
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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 (iT(reg)) cell- and T(H)17 cell-polarizing conditions in vitro. Further, Cyp26b1 expression was differentially regulated in iT(reg) and T(H)17 cells. Transfer of naive 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.
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