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Vitamin D treatment modulates immune activation in cystic fibrosis
Authors:T. Pincikova  D. Paquin‐Proulx  J. K. Sandberg  M. Flodström‐Tullberg  L. Hjelte
Affiliation:1. Stockholm CF Center, Karolinska University Hospital Huddinge, Stockholm, Sweden;2. Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden;3. Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenPresent address: T. Pincikova, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden;4. Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Abstract:Persistent inflammatory response in cystic fibrosis (CF) airways is believed to play a central role in the progression of lung damage. Anti‐inflammatory treatment may slow lung disease progression, but adverse side effects have limited its use. Vitamin D has immunoregulatory properties. We randomized 16 CF patients to receive vitamin D2, vitamin D3 or to serve as controls, and investigated the effect of vitamin D supplementation on soluble immunological parameters, myeloid dendritic cells (mDCs) and T cell activation. Three months of vitamin D treatment were followed by two washout months. Vitamin D status at baseline was correlated negatively with haptoglobin, erythrocyte sedimentation rate and immunoglobulin A concentration. Total vitamin D dose per kg bodyweight correlated with the down‐modulation of the co‐stimulatory receptor CD86 on mDCs. Vitamin D treatment was associated with reduced CD279 (PD‐1) expression on CD4+ and CD8+ T cells, as well as decreased frequency of CD8+ T cells co‐expressing the activation markers CD38 and human leucocyte antigen D‐related (HLA‐DR) in a dose‐dependent manner. There was a trend towards decreased mucosal‐associated invariant T cells (MAIT) cell frequency in patients receiving vitamin D and free serum 25‐hydroxyvitamin D (free‐s25OHD) correlated positively with CD38 expression by these cells. At the end of intervention, the change in free‐s25OHD was correlated negatively with the change in CD279 (PD‐1) expression on MAIT cells. Collectively, these data indicate that vitamin D has robust pleiotropic immunomodulatory effects in CF. Larger studies are needed to explore the immunomodulatory treatment potential of vitamin D in CF in more detail.
Keywords:cystic fibrosis  immunity  immunoglobulins  T cells  vitamin D
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