Swaminathan, Sanjay and Suzuki, Kazuo and Seddiki, Nabila and Kaplan, Warren and Cowley, Mark J and Hood, Chantelle L and Clancy, Jennifer L and Murray, Daniel D and Méndez, Catalina and Gelgor, Linda and Anderson, Ben and Roth, Norman and Cooper, David A and Kelleher, Anthony D (2012) Differential regulation of the Let-7 family of microRNAs in CD4+ T cells alters IL-10 expression. Journal of immunology (Baltimore, Md. : 1950), 188 (12). pp.6238-46. ISSN 1550-6606 (OA)
Full text not available from this repository.Abstract
MicroRNAs (miRNAs) are ∼22-nt small RNAs that are important regulators of mRNA turnover and translation. Recent studies have shown the importance of the miRNA pathway in HIV-1 infection, particularly in maintaining latency. Our initial in vitro studies demonstrated that HIV-1-infected HUT78 cells expressed significantly higher IL-10 levels compared with uninfected cultures. IL-10 plays an important role in the dysregulated cytotoxic T cell response to HIV-1, and in silico algorithms suggested that let-7 miRNAs target IL10 mRNA. In a time course experiment, we demonstrated that let-7 miRNAs fall rapidly following HIV-1 infection in HUT78 cells with concomitant rises in IL-10. To show a direct link between let-7 and IL-10, forced overexpression of let-7 miRNAs resulted in significantly reduced IL-10 levels, whereas inhibition of the function of these miRNAs increased IL-10. To demonstrate the relevance of these results, we focused our attention on CD4(+) T cells from uninfected healthy controls, chronic HIV-1-infected patients, and long-term nonprogressors. We characterized miRNA changes in CD4(+) T cells from these three groups and demonstrated that let-7 miRNAs were highly expressed in CD4(+) T cells from healthy controls and let-7 miRNAs were significantly decreased in chronic HIV-1 infected compared with both healthy controls and long-term nonprogressors. We describe a novel mechanism whereby IL-10 levels can be potentially modulated by changes to let-7 miRNAs. In HIV-1 infection, the decrease in let-7 miRNAs may result in an increase in IL-10 from CD4(+) T cells and provide the virus with an important survival advantage by manipulating the host immune response.
(Australian Government Department of Health and Ageing; NHMRC Grants 510448, 630571).
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 11 Jan 2016 04:55 |
| Last Modified: | 08 Mar 2016 00:34 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/159 |
Actions (login required)
 |
View Item |