1. IL-32 Drives the Differentiation of Cardiotropic CD4+ T Cells Carrying HIV DNA in People With HIV.
- Author
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Ramani, Hardik, Gosselin, Annie, Bunet, Rémi, Jenabian, Mohammad-Ali, Sylla, Mohamed, Pagliuzza, Amélie, Chartrand-Lefebvre, Carl, Routy, Jean-Pierre, Goulet, Jean-Philippe, Thomas, Réjean, Trottier, Benoit, Martel-Laferrière, Valérie, Fortin, Claude, Chomont, Nicolas, Fromentin, Rémi, Landay, Alan L, Durand, Madeleine, Ancuta, Petronela, El-Far, Mohamed, and Tremblay, Cecile
- Subjects
T cells ,HIV-positive persons ,INTERLEUKIN-32 ,PROTEIN-tyrosine kinases ,IMMUNOLOGIC memory ,VIRAL tropism - Abstract
Interleukin 32 (IL-32) is a potent multi-isoform proinflammatory cytokine, which is upregulated in people with HIV (PWH) and is associated with cardiovascular disease (CVD) risk. However, the impact of IL-32 isoforms on CD4 T-cell cardiotropism, a mechanism potentially contributing to heart inflammation, remains unknown. Here we show that IL-32 isoforms β and γ induce the generation of CCR4
+ CXCR3+ double positive (DP) memory CD4 T-cell subpopulation expressing the tyrosine kinase receptor c-Met, a phenotype associated with heart-homing of T cells. Our ex vivo studies on PWH show that the frequency of DP CD4 T cells is significantly higher in individuals with, compared to individuals without, subclinical atherosclerosis and that DP cells from antiretroviral-naive and treated individuals are highly enriched with HIV DNA. Together, these data demonstrate that IL-32 isoforms have the potential to induce heart-homing of HIV-infected CD4 T cells, which may further aggravate heart inflammation and CVD in PWH. [ABSTRACT FROM AUTHOR]- Published
- 2024
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