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Title: The Vitamin D Analog, TX527, Promotes a Human CD4+CD25highCD127low Regulatory T Cell Profile and Induces a Migratory Signature Specific for Homing to Sites of Inflammation
Authors: Baeke, Femke
Korf, Hannelie
Overbergh, Lutgart
Verstuyf, Annemieke
Thorrez, Lieven
Van Lommel, Leentje
Waer, Mark
Schuit, Frans
Gysemans, Conny
Mathieu, Chantal # ×
Issue Date: Jan-2011
Publisher: American Association of Immunologists
Series Title: Journal of Immunology vol:186 issue:1 pages:132-142
Abstract: The use of hypocalcemic vitamin D analogs is an appealing strategy to exploit the immunomodulatory actions of active vitamin D in vivo while circumventing its calcemic side effects. The functional modulation of dendritic cells by these molecules is regarded as the key mechanism underlying their ability to regulate T cell reactivity. In this article, we demonstrate the capacity of the vitamin D analog, TX527, to target T cells directly. Microarray analysis of purified human CD3(+) T cells, cultured in the presence of TX527, revealed differential expression of genes involved in T cell activation, proliferation, differentiation, and migratory capacity. Accordingly, functional analysis showed a TX527-mediated suppression of the T cell proliferative capacity and activation status, accompanied by decreased expression of effector cytokines (IFN-γ, IL-4, and IL-17). Furthermore, TX527 triggered the emergence of CD4(+)CD25(high)CD127(low) regulatory T cells featuring elevated levels of IL-10, CTLA-4, and OX40 and the functional capacity to suppress activation and proliferation of effector T cells. Moreover, the vitamin D analog profoundly altered the homing receptor profile of T cells and their migration toward chemokine ligands. Remarkably, TX527 not only modulated skin-homing receptors as illustrated for the parent compound, but also reduced the expression of lymphoid organ-homing receptors (CD62L, CCR7, and CXCR4) and uniquely promoted surface expression of inflammatory homing receptors (CCR5, CXCR3, and CXCR6) on T cells. We conclude that TX527 directly affects human T cell function, thereby inhibiting effector T cell reactivity while inducing regulatory T cell characteristics, and imprints them with a specific homing signature favoring migration to sites of inflammation.
URI: 
ISSN: 0022-1767
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
Interdepartemental Stem Cell Institute (-)
Gene Expression Unit
Laboratory of Experimental Transplantation
× corresponding author
# (joint) last author

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