title: 1,25-Dihydroxy-vitamin D3 regulates NK-cell cytotoxicity, cytokine secretion, and degranulation in women with recurrent pregnancy losses.
abstract: Vitamin D has a pivotal role in regulating immune responses by promoting Th2 immune responses and suppressing Th1 responses. Propensities to a Th1 immune response and increased NK-cell levels and cytotoxicity have been reported in women with recurrent pregnancy losses (RPL). In women with RPL, vitamin D deficiency is prevalent; however, the effect of vitamin D on NK cells is largely unknown. In this study, we demonstrated that CD69(+) activating receptor expression on NK cells was significantly decreased by incubation with 1,25(OH)2 D3 in a dose-dependent manner, while CD158a and CD158b inhibitory receptor expression was upregulated. The degranulation marker CD107a was significantly downregulated on NK cells following incubation with 1,25(OH)2 D3 . NK-cell conjugation with K562 target cells was not affected by 1,25(OH)2 D3 ; however, depolarization of perforin granules in conjugated NK cells was significantly increased. TLR4 expression on NK cells was significantly decreased and TNF-α and IFN-γ production was significantly reduced by 1,25(OH)2 D3 through interference with NF-κB. Our results suggest 1,25(OH)2 D3 has immune regulatory effects on NK cell cytotoxicity, cytokine secretion and degranulation process as well as TLR4 expression. Potential therapeutic application of 1,25(OH)2 D3 for dysregulated NK-cell immunity should be explored in the future.
authors.affiliation: Department of Microbiology and Immunology, Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.|Reproductive Medicine, Department of Obstetrics and Gynecology, Chicago Medical School at Rosalind Franklin University of Medicine and Science, Vernon Hills, IL, USA.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Ota
authors.affiliation: Department of Microbiology and Immunology, Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Dambaeva
authors.affiliation: Department of Microbiology and Immunology, Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
authors.forename: Michael Woo-Il
authors.initials: MW
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.|Reproductive Medicine, Department of Obstetrics and Gynecology, Chicago Medical School at Rosalind Franklin University of Medicine and Science, Vernon Hills, IL, USA.
authors.forename: Ae-Ra
authors.initials: AR
authors.lastname: Han
authors.affiliation: Department of Obstetrics and Gynecology, Hirosaki University School of Medicine, Hirosaki, Aomori, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukui
authors.affiliation: Department of Microbiology and Immunology, Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Gilman-Sachs
authors.affiliation: Department of Microbiology and Immunology, Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Beaman
authors.affiliation: Department of Microbiology and Immunology, Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.|Reproductive Medicine, Department of Obstetrics and Gynecology, Chicago Medical School at Rosalind Franklin University of Medicine and Science, Vernon Hills, IL, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Kwak-Kim
mesh_terms: D000026:Abortion, Habitual / Q000276:immunology*; D000328:Adult; D016207:Cytokines / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D011247:Pregnancy; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D016207:Cytokines; C118756:dihydroxy-vitamin D3; D014807:Vitamin D
keywords: 1,25(OH)2D3; Cytokines; Cytotoxicity; Natural killer cell; Pregnancy; Vitamin D