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Dysregulated miR-15...
Dysregulated miR-155 and miR-125b are related to impaired B-cell responses in down syndrome
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Farroni, C. (author)
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Marasco, E. (author)
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Marcellini, V. (author)
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Giorda, E. (author)
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Valentini, D. (author)
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Petrini, S. (author)
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D'Oria, V. (author)
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Pezzullo, M. (author)
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Cascioli, S. (author)
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Scarsella, M. (author)
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Ugazio, A. G. (author)
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De Vincentiis, G. C. (author)
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- Grimsholm, Ola, 1979 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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Carsetti, R. (author)
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(creator_code:org_t)
- 2018-11-20
- 2018
- English.
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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9
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https://gup.ub.gu.se...
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https://doi.org/10.3...
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Abstract
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- AntagomiR
- B cell
- Down Syndrome
- Germinal center
- Immunodeficiency
- MiR-125b
- MiR-155
- Plasma cells
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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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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show more...
-
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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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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Frontiers in Imm ...
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University of Gothenburg