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Evaluation of calcitriol and its analogues for its effect on the DC differentiation/activation pathway induced by type I IFN

signalling dataset

We obtained data on the Pharmacological compound 1alpha,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the biologically active metabolite of Vitamin D3, and its analogues, and its effect on the DC differentiation/activation pathway induced by type I IFN. 1,25(OH)2D3 prevented the generation of IFN-DCs when added to freshly isolated monocytes, and is capable to redirect already differentiated IFN-DCs toward a more immature stage. Interestingly the suppressive effect of 1,25(OH)2D3 was associated with a potent impairment of DC migration in response to inflammatory and lymph node homing chemokines, thus unraveling a novel mechanism involved in 1,25(OH)2D3-mediated immunomodulation. Experiments to characterise the molecular mechanisms underlining this inhibitory effect, including the expression of ILT-receptors and a panel of adhesion molecules known for their role in leukocyte migration are ongoing. Further studies are focussed on the dissection of the signal transduction pathway of 1,25(OH)2D3 in DCs, and on its interference with chemokine receptor signalling.





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