AUTHOR=Chitnis Nilesh , Clark Peter M. , Kamoun Malek , Stolle Catherine , Brad Johnson F. , Monos Dimitri S. 

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

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00583

DOI=10.3389/fimmu.2017.00583

ISSN=1664-3224

ABSTRACT=<p>We describe a novel functional role for the <italic>HLA-B</italic> locus mediated by its intron-encoded microRNA (miRNA), miR-6891-5p. We show that <italic>in vitro</italic> 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 (<italic>IGHA1</italic> and <italic>IGHA2</italic>) transcripts and demonstrated that this miRNA modulates the expression of <italic>IGHA1</italic> and <italic>IGHA2</italic>. 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 <italic>IGHA1</italic> and <italic>IGHA2</italic> gene expression at the posttranscriptional level and suggest that increase in miR-6891-5p levels may contribute to the etiology of selective IgA deficiency.</p>