Journal article

Vitamin D increases glucocorticoid efficacy via inhibition of mTORC1 in experimental models of multiple sclerosis

Robert Hoepner, Maud Bagnoud, Maximilian Pistor, Anke Salmen, Myriam Briner, Helen Synn, Lisa Schrewe, Kirsten Guse, Farhad Ahmadi, Seray Demir, Louis Laverick, Melissa Gresle, Paul Worley, Holger Michael Reichardt, Helmut Butzkueven, Ralf Gold, Imke Metz, Fred Luehder, Andrew Chan

Acta Neuropathologica | SPRINGER | Published : 2019

Abstract

The limited efficacy of glucocorticoids (GCs) during therapy of acute relapses in multiple sclerosis (MS) leads to long-term disability. We investigated the potential of vitamin D (VD) to enhance GC efficacy and the mechanisms underlying this VD/GC interaction. In vitro, GC receptor (GR) expression levels were quantified by ELISA and induction of T cell apoptosis served as a functional readout to assess synergistic 1,25(OH)2D3 (1,25D)/GC effects. Experimental autoimmune encephalomyelitis (MOG35-55 EAE) was induced in mice with T cell-specific GR or mTORc1 deficiency. 25(OH)D (25D) levels were determined in two independent cohorts of MS patients with stable disease or relapses either responsi..

View full abstract

Grants

Awarded by Swiss National Fund (SNF)


Awarded by NHMRC


Awarded by NHRMC Practitioner Fellowship


Funding Acknowledgements

This work was funded by the Swiss National Fund (SNF no. 310030_172952). Parts of the work (human gene analyses) were also supported by NHMRC Project Grant 1032486, NHRMC Practitioner Fellowship (Level A; 1080518; HB) and the MS Research Australia Fellow Ship, which supported MMG.