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Dysregulated miR-15...
Dysregulated miR-155 and miR-125b are related to impaired B-cell responses in down syndrome
- Article/chapterEnglish2018
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2018-11-20
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Frontiers Media SA,2018
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LIBRIS-ID:oai:gup.ub.gu.se/273977
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https://gup.ub.gu.se/publication/273977URI
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https://doi.org/10.3389/fimmu.2018.02683DOI
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Subject category:art swepub-publicationtype
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Children with Down Syndrome (DS) suffer from immune deficiency with a severe reduction in switched memory B cells (MBCs) and poor response to vaccination. Chromosome 21 (HSA21) encodes two microRNAs (miRs), miR-125b, and miR-155, that regulate B-cell responses. We studied B- and T- cell subpopulations in tonsils of DS and age-matched healthy donors (HD) and found that the germinal center (GC) reaction was impaired in DS. GC size, numbers of GC B cells and Follicular Helper T cells (TFH) expressing BCL6 cells were severely reduced. The expression of miR-155 and miR-125b was increased in tonsillar memory B cells and miR-125b was also higher than expected in plasma cells (PCs). Activation-induced cytidine deaminase (AID) protein, a miR-155 target, was significantly reduced in MBCs of DS patients. Increased expression of miR-155 was also observed in vitro. MiR-155 was significantly overexpressed in PBMCs activated with CpG, whereas miR-125b was constitutively higher than normal. The increase of miR-155 and its functional consequences were blocked by antagomiRs in vitro. Our data show that the expression of HSA21-encoded miR-155 and miR-125b is altered in B cells of DS individuals both in vivo and in vitro. Because of HSA21-encoded miRs may play a role also in DS-associated dementia and leukemia, our study suggests that antagomiRs may represent pharmacological tools useful for the treatment of DS. © 2007 - 2018 Frontiers Media S.A. All Rights Reserved.
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Marasco, E.
(author)
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Marcellini, V.
(author)
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Giorda, E.
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Valentini, D.
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Petrini, S.
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D'Oria, V.
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Pezzullo, M.
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Cascioli, S.
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Scarsella, M.
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Ugazio, A. G.
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De Vincentiis, G. C.
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Grimsholm, Ola,1979Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xgriol
(author)
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Carsetti, R.
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Göteborgs universitetInstitutionen för medicin, avdelningen för reumatologi och inflammationsforskning
(creator_code:org_t)
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In:Frontiers in Immunology: Frontiers Media SA91664-3224
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Farroni, C.
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Marasco, E.
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Marcellini, V.
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Giorda, E.
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Valentini, D.
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Petrini, S.
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D'Oria, V.
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Pezzullo, M.
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Cascioli, S.
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Scarsella, M.
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Ugazio, A. G.
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De Vincentiis, G ...
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Grimsholm, Ola, ...
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Carsetti, R.
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- MEDICAL AND HEALTH SCIENCES
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Frontiers in Imm ...
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University of Gothenburg