title: 1,25-Dihydroxyvitamin D3 and its analog TX527 promote a stable regulatory T cell phenotype in T cells from type 1 diabetes patients.
abstract: The emergence of regulatory T cells (Tregs) as central mediators of peripheral tolerance in the immune system has led to an important area of clinical investigation to target these cells for the treatment of autoimmune diseases such as type 1 diabetes. We have demonstrated earlier that in vitro treatment of T cells from healthy individuals with TX527, a low-calcemic analog of bioactive vitamin D, can promote a CD4+ CD25high CD127low regulatory profile and imprint a migratory signature specific for homing to sites of inflammation. Towards clinical application of vitamin D-induced Tregs in autologous adoptive immunotherapy for type 1 diabetes, we show here that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and TX527 similarly imprint T cells from type 1 diabetes patients with a CD4+ CD25high CD127low regulatory profile, modulate surface expression of skin- and inflammation-homing receptors, and increase expression of CTLA-4 and OX-40. Also, 1,25(OH)2D3 and TX527 treatment inhibit the production of effector cytokines IFN-γ, IL-9, and IL-17. Importantly, 1,25(OH)2D3 and TX527 promote the induction of IL-10-producing CD4+ CD25high CD127low T cells with a stable phenotype and the functional capacity to suppress proliferation of autologous responder T cells in vitro. These findings warrant additional validation of vitamin D-induced Tregs in view of future autologous adoptive immunotherapy in type 1 diabetes.
authors.affiliation: Clinical and Experimental Endocrinology (CEE), KU Leuven, Leuven, Belgium.
authors.forename: Tom L
authors.initials: TL
authors.lastname: Van Belle
authors.affiliation: Clinical and Experimental Endocrinology (CEE), KU Leuven, Leuven, Belgium.
authors.forename: An-Sofie
authors.initials: AS
authors.lastname: Vanherwegen
authors.affiliation: Clinical and Experimental Endocrinology (CEE), KU Leuven, Leuven, Belgium.
authors.forename: Dorien
authors.initials: D
authors.lastname: Feyaerts
authors.affiliation: Laboratory for Organic Synthesis, Department of Organic Chemistry, Ghent University, Ghent, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: De Clercq
authors.affiliation: Clinical and Experimental Endocrinology (CEE), KU Leuven, Leuven, Belgium.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Verstuyf
authors.affiliation: Clinical and Experimental Endocrinology (CEE), KU Leuven, Leuven, Belgium.
authors.forename: Hannelie
authors.initials: H
authors.lastname: Korf
authors.affiliation: Clinical and Experimental Endocrinology (CEE), KU Leuven, Leuven, Belgium.
authors.forename: Conny
authors.initials: C
authors.lastname: Gysemans
authors.affiliation: Clinical and Experimental Endocrinology (CEE), KU Leuven, Leuven, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
mesh_terms: D000480:Alkynes / Q000494:pharmacology*; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D002762:Cholecalciferol / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D006801:Humans; D010641:Phenotype; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
chemical_list: D000480:Alkynes; C409043:inecalcitol; D002762:Cholecalciferol; D002117:Calcitriol