Dysregulated miR-155 and miR-125b Are Related to Impaired B-cell Responses in Down Syndrome.

Front Immunol 2018 20;9:2683. Epub 2018 Nov 20.

B cell Pathophysiology Unit, Immunology Research Area, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

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 (T) 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 . 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 . Our data show that the expression of HSA21-encoded miR-155 and miR-125b is altered in B cells of DS individuals both and . 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.

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Source
https://www.frontiersin.org/article/10.3389/fimmu.2018.02683
Publisher Site
http://dx.doi.org/10.3389/fimmu.2018.02683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255899PMC
October 2019
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