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Vitamin D treatment modulates immune activation in cystic fibrosis.

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.

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    ,

    Stockholm CF Center, Karolinska University Hospital Huddinge, Stockholm, Sweden. Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

    ,

    Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

    ,

    Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

    ,

    Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

    Stockholm CF Center, Karolinska University Hospital Huddinge, Stockholm, Sweden. Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

    Source

    Clinical and experimental immunology 189:3 2017 09 pg 359-371

    MeSH

    ADP-ribosyl Cyclase 1
    Adolescent
    B7-2 Antigen
    CD4-Positive T-Lymphocytes
    CD8-Positive T-Lymphocytes
    Child
    Cholecalciferol
    Cystic Fibrosis
    Dendritic Cells
    Dietary Supplements
    Ergocalciferols
    Female
    HLA-DR Antigens
    Haptoglobins
    Humans
    Immunomodulation
    Lymphocyte Activation
    Male
    Membrane Glycoproteins
    Pilot Projects
    Programmed Cell Death 1 Receptor
    Pseudomonas aeruginosa
    Vitamin D

    Pub Type(s)

    Clinical Trial
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    28470739

    Citation

    Pincikova, T, et al. "Vitamin D Treatment Modulates Immune Activation in Cystic Fibrosis." Clinical and Experimental Immunology, vol. 189, no. 3, 2017, pp. 359-371.
    Pincikova T, Paquin-Proulx D, Sandberg JK, et al. Vitamin D treatment modulates immune activation in cystic fibrosis. Clin Exp Immunol. 2017;189(3):359-371.
    Pincikova, T., Paquin-Proulx, D., Sandberg, J. K., Flodström-Tullberg, M., & Hjelte, L. (2017). Vitamin D treatment modulates immune activation in cystic fibrosis. Clinical and Experimental Immunology, 189(3), pp. 359-371. doi:10.1111/cei.12984.
    Pincikova T, et al. Vitamin D Treatment Modulates Immune Activation in Cystic Fibrosis. Clin Exp Immunol. 2017;189(3):359-371. PubMed PMID: 28470739.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Vitamin D treatment modulates immune activation in cystic fibrosis. AU - Pincikova,T, AU - Paquin-Proulx,D, AU - Sandberg,J K, AU - Flodström-Tullberg,M, AU - Hjelte,L, Y1 - 2017/05/24/ PY - 2017/04/19/accepted PY - 2017/5/5/pubmed PY - 2017/10/17/medline PY - 2017/5/5/entrez KW - T cells KW - cystic fibrosis KW - immunity KW - immunoglobulins KW - vitamin D SP - 359 EP - 371 JF - Clinical and experimental immunology JO - Clin. Exp. Immunol. VL - 189 IS - 3 N2 - 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. SN - 1365-2249 UR - https://www.unboundmedicine.com/medline/citation/28470739/Vitamin_D_treatment_modulates_immune_activation_in_cystic_fibrosis_ L2 - https://doi.org/10.1111/cei.12984 DB - PRIME DP - Unbound Medicine ER -