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An Expanded Role for HLA Genes: HLA-B Encodes a microRNA that Regulates IgA and Other Immune Response Transcripts
Journal article   Open access   Peer reviewed

An Expanded Role for HLA Genes: HLA-B Encodes a microRNA that Regulates IgA and Other Immune Response Transcripts

Nilesh Chitnis, Peter M. Clark, Malek Kamoun, Catherine Stolle, F. Brad Johnson and Dimitri S. Monos
Frontiers in immunology, v 8(MAY), pp 583-583
19 May 2017
PMID: 28579988
url
https://www.frontiersin.org/articles/10.3389/fimmu.2017.00583/pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.3389/fimmu.2017.00583View
Published, Version of Record (VoR) Open

Abstract

B lymphocyte HLA-B Immunology miR-6891-5p mirtron primary immunodeficiency selective IgA deficiency
We describe a novel functional role for the HLA-B locus mediated by its intron-encoded microRNA (miRNA), miR-6891-5p. We show that in vitro inhibition of miR-6891-5p impacts the expression of nearly 200 transcripts within the B-lymphoblastoid cell line (B-LCL) COX, affecting a large number of metabolic pathways, including various immune response networks. The top affected transcripts following miR-6891-5p inhibition are those encoding the heavy chain of IgA. We identified a conserved miR-6891-5p target site on the 3′UTR of both immunoglobulin heavy chain alpha 1 and 2 ( IGHA1 and IGHA2 ) transcripts and demonstrated that this miRNA modulates the expression of IGHA1 and IGHA2 . B-LCLs from IgA-deficient patients expressed significantly elevated levels of miR-6891-5p when compared with unaffected family members. Upon inhibition of miR-6891-5p, IgA mRNA expression levels were increased, and IgA secretion was restored in the B-LCL of an IgA-deficient patient. These findings indicate that miR-6891-5p regulates IGHA1 and IGHA2 gene expression at the posttranscriptional level and suggest that increase in miR-6891-5p levels may contribute to the etiology of selective IgA deficiency.

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Immunology
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