The microRNA‐9/B‐lymphocyte‐induced maturation protein‐1/IL‐2 axis is differentially regulated in progressive HIV infection. Issue 2 (18th December 2012)

• Record Type: Journal Article
• Authors: Seddiki, Nabila; Phetsouphanh, Chansavath; Swaminathan, Sanjay; Xu, Yin; Rao, Sudha; Li, Jasmine; Sutcliffe, Elissa L.; Denyer, Gareth; Finlayson, Robert; Gelgor, Linda; Cooper, David A.; Zaunders, John; Kelleher, Anthony D.
• Is Part Of: European journal of immunology. Volume 43:Issue 2(2013:Feb.)
• Page Start: 510
• Page End: 520
• Publication Date: 2012-12-18
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201242695
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The fine control of T‐cell differentiation and its impact on HIV disease states is poorly understood. In this study, we demonstrate that B‐lymphocyte‐induced maturation protein‐1 (Blimp‐1/<italic>Prdm1</italic>) is highly expressed in CD4⁺ T cells from chronically HIV‐infected (CHI) patients compared to cells from long‐term nonprogressors or healthy controls. Stimulation through the T‐cell receptor in the presence ofIL‐2 induces Blimp‐1 protein expression. We show here that Blimp‐1 levels are translationally regulated by microRNA‐9 (miR‐9). Overexpression of miR‐9 induces Blimp‐1 repression, restoring IL‐2 secretion in CD4⁺ T cells via reduction in the binding of Blimp‐1 to the <italic>il‐2</italic> promoter. In CHI patients where IL‐2 expression is reduced and there is generalized T‐cell dysfunction, we show differential expression of both miR‐9 and Blimp‐1 in CD4⁺ cells compared with levels in long‐term nonprogressors. These data identify a novel miR‐9/Blimp‐1/IL‐2 axis that is dysregulated in progressive HIV infection.</p> </abstract>