Dysregulated miR-155 and miR-125b are related to impaired B-cell responses in down syndrome

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.

Marasco, E. (författare)
Marcellini, V. (författare)
Giorda, E. (författare)
Valentini, D. (författare)
Petrini, S. (författare)
D'Oria, V. (författare)
Pezzullo, M. (författare)
Cascioli, S. (författare)
Scarsella, M. (författare)
Ugazio, A. G. (författare)
De Vincentiis, G. C. (författare)
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 (författare)
Carsetti, R. (författare)
Göteborgs universitetInstitutionen för medicin, avdelningen för reumatologi och inflammationsforskning (creator_code:org_t)

Av författaren/redakt...: Farroni, C.; Marasco, E.; Marcellini, V.; Giorda, E.; Valentini, D.; Petrini, S.; visa fler...; D'Oria, V.; Pezzullo, M.; Cascioli, S.; Scarsella, M.; Ugazio, A. G.; De Vincentiis, G ...; Grimsholm, Ola, ...; Carsetti, R.; visa färre...

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