1,25-dihydroxyvitamin D3 and dexamethasone increase interleukin-10 production in CD4+ T cells from patients with Crohn's disease

Bartels, Lars Erik; Jørgensen, Søren Peter; Agnholt, Jørgen; Kelsen, Jens; Hvas, Christian Lodberg; Dahlerup, Jens Frederik

doi:10.1016/j.intimp.2007.09.016

Cited by 66 publications

(52 citation statements)

References 36 publications

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“…Furthermore, the synthetic agonist also effectively inhibited Th1, Th17, as well as Th2 reactivity of the cells. Up to now, varying results regarding the direct effects of active vitamin D metabolites on T cell cytokine responses have been reported, with a majority of studies showing inhibitory effects on Th1 (IFN-g) and Th17 responses (IL-17), whereas Th2 (IL-4) was mostly shown to be stable or increased under unpolarized conditions in studies using mouse T cells (11)(12)(13) or human T cells (14,(26)(27)(28)(29). However, in our hands, triggering of VDR signaling by the hypocalcemic vitamin D analog TX527 resulted in an overall inhibition of T effector cytokine responses, including Th2 cytokines.…”

Section: Discussionmentioning

confidence: 99%

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

Baeke

Korf

Overbergh

et al. 2011

The Journal of Immunology

118

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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+CD25highCD127low 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.

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Section: Discussionmentioning

confidence: 99%

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

Baeke

Korf

Overbergh

et al. 2011

The Journal of Immunology

118

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“…874 % of recommended daily allowance, RDA) and vitamin E, previously induced with-in group reduction of IBD-related joint pain [24]. Interestingly, mice lacking vitamin D receptor develop experimental colitis, and it has been suggested that vitamin D deficiency may increase the risk of IBD [52] and that vitamin D supplementation may be beneficial in CD patients [53]. In the present study, WO or SO provided 4.3 g or 0.8 g vitamin D/day, 57 or 11 % of RDA respectively.…”

Section: Discussionmentioning

confidence: 99%

A randomized double blind comparison of short-term duodenally administrated whale and seal blubber oils in patients with inflammatory bowel disease and joint pain

Bjørkkjær

Araujo²,

Madland

et al. 2009

Prostaglandins, Leukotrienes and Essential Fatty Acids

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“…There is new interest, however, in vitamin D in IBD 'beyond bone' as a treatment for the core inflammatory disease. Growing evidence from epidemiological studies, animal models, cross-sectional studies and some intervention studies appear to support such a role (11)(12)(13)(14)(15) . The aim of this review is to critically evaluate several strands of scientific evidence surrounding vitamin D and inflammation in autoimmune diseases, primarily focusing on IBD and to understand how this translates to disease management.…”

Section: Proceedings Of the Nutrition Societymentioning

confidence: 99%

Vitamin D as a novel therapy in inflammatory bowel disease: new hope or false dawn?

O’Sullivan

2014

Proc. Nutr. Soc.

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There is increasing scientific interest in the field of vitamin D research, moving the focus beyond bone health to other disease processes. Low circulating vitamin D levels have been reported as a risk factor for several pathophysiologically divergent diseases, including cancers, diabetes, CVD, multiple sclerosis and inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease (IBD). But, therein, remains the challenge: can any single nutrient contribute to multiple complex disease mechanisms and, ultimately, have therapeutic potential? The aim of this review is to critically evaluate several strands of scientific evidence surrounding vitamin D and inflammation, primarily focusing on IBD. Epidemiological studies suggest an increased incidence of IBD and rheumatoid arthritis in countries of more northern latitudes, mirroring sunlight patterns. A considerable body of evidence supports the anti-inflammatory effects of vitamin D, at least in animal models of IBD. Although it is accepted that suboptimal vitamin D status is common in IBD, some studies suggest that this associates with more severe disease. With regard to treatment, the data are only beginning to emerge from randomised controlled trials to suggest that people with IBD may remain in remission longer when treated with oral vitamin D. In conclusion, several strands of evidence suggest that vitamin D may modify the immune response in IBD. There is a continued need for large well-designed clinical trials and mechanistic studies to determine if, and how, this emerging promise translates into tangible clinical benefits for people with chronic debilitating diseases such as IBD.

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1,25-dihydroxyvitamin D3 and dexamethasone increase interleukin-10 production in CD4+ T cells from patients with Crohn's disease

Cited by 66 publications

References 36 publications

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

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

A randomized double blind comparison of short-term duodenally administrated whale and seal blubber oils in patients with inflammatory bowel disease and joint pain

Vitamin D as a novel therapy in inflammatory bowel disease: new hope or false dawn?

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