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2014 ; 143
(1
): 52-60
Nephropedia Template TP
gab.com Text
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English Wikipedia
1?,25-dihydroxyvitamin D3 in combination with transforming growth factor-?
increases the frequency of Foxp3? regulatory T cells through preferential
expansion and usage of interleukin-2
#MMPMID24673126
Chambers ES
; Suwannasaen D
; Mann EH
; Urry Z
; Richards DF
; Lertmemongkolchai G
; Hawrylowicz CM
Immunology
2014[Sep]; 143
(1
): 52-60
PMID24673126
show ga
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?,25-dihydroxyvitamin D3 [1,25(OH)2D3], 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)2D3 at more
moderate concentrations (10(-7) M). Stimulation of human CD4(+) T cells with a
combination of 1,25(OH)2D3 and transforming growth factor-? (TGF-?) 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-? in the presence of 1,25(OH)2D3(10(-7) M)
significantly increased Foxp3(+) Treg cell frequency. These data provide
additional evidence for the important immunomodulatory properties of 1,25(OH)2D3
that exist and may help to control inflammatory diseases.