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1 α ,25‐dihydroxyvitamin D3 in combination with transforming growth factor‐ β increases the frequency of Foxp3 + regulatory T cells through preferential expansion and usage of interleukin‐2
A high prevalence of vitamin D insufficiency and deficiency exists worldwide, which is associated with an increased incidence and severity of a range of immune‐mediated diseases. This has resulted in considerable interest in the immunodulatory functions of vitamin D. The active form of vitamin D, 1...
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Published in: | Immunology 2014-09, Vol.143 (1), p.52-60 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | A high prevalence of vitamin D insufficiency and deficiency exists worldwide, which is associated with an increased incidence and severity of a range of immune‐mediated diseases. This has resulted in considerable interest in the immunodulatory functions of vitamin D. The active form of vitamin D, 1
α
,25‐dihydroxyvitamin D3 [1,25(
OH
)
2
D3], has been shown to increase the frequency of Foxp3
+
CD4
+
T regulatory (Treg) cells when present at high concentrations or under strong T‐cell stimulation in culture. Supporting evidence exists
in vivo
for a positive association between serum 25(
OH
)D and Foxp3
+
Treg cell numbers in humans. The aim of this work was to identify the cytokine milieu required
in vitro
to promote Foxp3
+
Treg cells in cultures containing 1,25(
OH
)
2
D3 at more moderate concentrations (10
−7
m
). Stimulation of human
CD
4
+
T cells with a combination of 1,25(
OH
)
2
D3 and transforming growth factor‐
β
(
TGF
‐
β
) greatly increased the frequency of Foxp3
+
Treg cells, which is proposed to result from the preferential expansion of Foxp3
+
Treg cells, as compared with the Foxp3
−
effector T cells, in culture. The differential effect on proliferation may result from enhanced availability and usage of interleukin‐2 by the Foxp3
+
Treg cells compared with Foxp3
−
effector T cells. In summary, modulation of the cytokine environment to one high in
TGF
‐
β
in the presence of 1,25(
OH
)
2
D3 (10
−7
m
) significantly increased Foxp3
+
Treg cell frequency. These data provide additional evidence for the important immunomodulatory properties of 1,25(
OH
)
2
D3 that exist and may help to control inflammatory diseases. |
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ISSN: | 0019-2805 1365-2567 |
DOI: | 10.1111/imm.12289 |