title: Interleukin-7 expression and its effect on natural killer cells in patients with multiple sclerosis.
abstract: Decreased NK cell numbers and impairment of NK cell function are reported in patients with multiple sclerosis (MS). Interleukin-7 (IL-7) is a member of the common gamma-chain (γc) cytokine superfamily that has well documented roles in lymphocyte development and homeostasis. The interleukin-7 receptor α chain (IL-7Rα) gene was identified as a top non-major histocompatibility complex-linked risk locus for MS. The objective of this study was to test biological function of IL-7/IL-7Rα on NK cells in MS patients. We observed markedly lower IL-7 levels in MS sera, and relatively higher IL-7Rα expression in NK cells of MS. Upon IL-7 stimulation, IL-7Rα on NK cells from MS patients was significantly down-regulated compared with healthy controls (HCs). IL-7 induced a higher increase of IFN-γ production in CD56(bright) NK cells and a pronounced enhancement of cytotoxicity in NK cells from MS. IL-7 did not impact the proliferation of NK cells differently in MS and HC. In contrast, IL-7 promoted a higher survival of CD56(bright) NK cells in MS and inhibited their apoptosis by increasing Bcl-2 expression, but had no effect on CD56(dim) NK cell survival in MS. In conclusion, MS patients have lower serum IL-7 and a higher membrane IL-7Rα expression on CD56(bright) NK cells. The skew at the IL-7 and IL-7Rα level influences functional responsiveness of NK cells in MS.
authors.affiliation: Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, United States; Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Su
authors.affiliation: Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, United States.
authors.forename: Samuel X
authors.initials: SX
authors.lastname: Shi
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, United States.
authors.forename: Aimee
authors.initials: A
authors.lastname: Borazanci
authors.affiliation: Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, United States; Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: fshi@tijmu.edu.cn.
authors.forename: Fu-Dong
authors.initials: FD
authors.lastname: Shi
authors.affiliation: Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, United States. Electronic address: ygan@grhc.org.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gan
mesh_terms: D000704:Analysis of Variance; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003609:Dactinomycin / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015851:Interleukin-7 / Q000097:blood* / Q000494:pharmacology; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood* / Q000473:pathology*
chemical_list: D017304:Annexin A5; D019002:CD56 Antigen; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D003609:Dactinomycin; C025942:7-aminoactinomycin D; D001973:Bromodeoxyuridine
keywords: CD56(bright); CD56(dim); IL-7; IL-7Rα; Multiple sclerosis; Natural killer cells