IL-32 Drives the Differentiation of Cardiotropic CD4+ T Cells Carrying HIV DNA in People With HIV

Hardik Ramani; Annie Gosselin; Rémi Bunet; Mohammad Ali Jenabian; Mohamed Sylla; Amélie Pagliuzza; Carl Chartrand-Lefebvre; Jean Pierre Routy; Jean Philippe Goulet; Réjean Thomas; Benoit Trottier; Valérie Martel-Laferrière; Claude Fortin; Nicolas Chomont; Rémi Fromentin; Alan L. Landay; Madeleine Durand; Petronela Ancuta; Mohamed El-Far; Cecile Tremblay

doi:10.1093/infdis/jiad576

IL-32 Drives the Differentiation of Cardiotropic CD4⁺ T Cells Carrying HIV DNA in People With HIV

Hardik Ramani
, Annie Gosselin
, Rémi Bunet
, Mohammad Ali Jenabian
, Mohamed Sylla
, Amélie Pagliuzza
, Carl Chartrand-Lefebvre
, Jean Pierre Routy
, Jean Philippe Goulet
, Réjean Thomas
, Benoit Trottier
, Valérie Martel-Laferrière
, Claude Fortin
, Nicolas Chomont
, Rémi Fromentin
, Alan L. Landay
, Madeleine Durand
, Petronela Ancuta
, Mohamed El-Far
, Cecile Tremblay

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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 γinduce 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.

Original language	English (US)
Pages (from-to)	1277-1289
Number of pages	13
Journal	Journal of Infectious Diseases
Volume	229
Issue number	5
DOIs	https://doi.org/10.1093/infdis/jiad576
State	Published - May 15 2024
Externally published	Yes

Keywords

CD4 T cells
HIV
IL-32
cardiovascular disease
heart-homing
inflammation

ASJC Scopus subject areas

Immunology and Allergy
Infectious Diseases

Access to Document

10.1093/infdis/jiad576

Cite this

Ramani, H., Gosselin, A., Bunet, R., Jenabian, M. A., Sylla, M., Pagliuzza, A., Chartrand-Lefebvre, C., Routy, J. P., Goulet, J. P., Thomas, R., Trottier, B., Martel-Laferrière, V., Fortin, C., Chomont, N., Fromentin, R., Landay, A. L., Durand, M., Ancuta, P., El-Far, M., & Tremblay, C. (2024). IL-32 Drives the Differentiation of Cardiotropic CD4⁺ T Cells Carrying HIV DNA in People With HIV. Journal of Infectious Diseases, 229(5), 1277-1289. https://doi.org/10.1093/infdis/jiad576

Ramani, H, Gosselin, A, Bunet, R, Jenabian, MA, Sylla, M, Pagliuzza, A, Chartrand-Lefebvre, C, Routy, JP, Goulet, JP, Thomas, R, Trottier, B, Martel-Laferrière, V, Fortin, C, Chomont, N, Fromentin, R, Landay, AL, Durand, M, Ancuta, P, El-Far, M & Tremblay, C 2024, 'IL-32 Drives the Differentiation of Cardiotropic CD4⁺ T Cells Carrying HIV DNA in People With HIV', Journal of Infectious Diseases, vol. 229, no. 5, pp. 1277-1289. https://doi.org/10.1093/infdis/jiad576

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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 γinduce 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.",

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AU - El-Far, Mohamed

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AB - 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 γinduce 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.

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