IL-27 induces IFN/STAT1-dependent genes and enhances function of TIGIT+ HIVGag-specific T cells

Jie Cheng; Timothy G. Myers; Callie Levinger; Princy Kumar; Jai Kumar; Bruktawit A. Goshu; Alberto Bosque; Marta Catalfamo

iScience (Jan 2022)

IL-27 induces IFN/STAT1-dependent genes and enhances function of TIGIT+ HIVGag-specific T cells

Jie Cheng,
Timothy G. Myers,
Callie Levinger,
Princy Kumar,
Jai Kumar,
Bruktawit A. Goshu,
Alberto Bosque,
Marta Catalfamo

Affiliations

Jie Cheng: Department of Microbiology and Immunology, Georgetown University School of Medicine, 3970 Reservoir Road, N.W, New Research Building, Room EG19A, Washington, DC 20057, USA
Timothy G. Myers: Genomic Technologies Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Callie Levinger: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine & Health Sciences, George Washington University, Washington, DC 20037, USA
Princy Kumar: Division of Infectious Diseases and Travel Medicine, Georgetown University School of Medicine, Washington, DC 20057, USA
Jai Kumar: Division of Infectious Diseases and Travel Medicine, Georgetown University School of Medicine, Washington, DC 20057, USA
Bruktawit A. Goshu: Department of Microbiology and Immunology, Georgetown University School of Medicine, 3970 Reservoir Road, N.W, New Research Building, Room EG19A, Washington, DC 20057, USA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Alberto Bosque: Department of Microbiology, Immunology and Tropical Medicine, School of Medicine & Health Sciences, George Washington University, Washington, DC 20037, USA
Marta Catalfamo: Department of Microbiology and Immunology, Georgetown University School of Medicine, 3970 Reservoir Road, N.W, New Research Building, Room EG19A, Washington, DC 20057, USA; Corresponding author

Journal volume & issue: Vol. 25, no. 1
p. 103588

Abstract

Read online

Summary: HIV-specific T cells have diminished effector function and fail to control/eliminate the virus. IL-27, a member of the IL-6/IL-12 cytokine superfamily has been shown to inhibit HIV replication. However, whether or not IL-27 can enhance HIV-specific T cell function is largely unknown. In the present manuscript, we investigated the role of IL-27 signaling in human T cells by evaluating the global transcriptional changes related to the function of HIV-specific T cells. We found that T cells from people living with HIV (PLWH), expressed higher levels of STAT1 leading to enhanced STAT1 activation upon IL-27 stimulation. Observed IL-27 induced transcriptional changes were associated with IFN/STAT1-dependent pathways in CD4 and CD8 T cells. Importantly, IL-27 dependent modulation of T-bet expression promoted IFNγ secretion by TIGIT+HIVGag-specific T cells. This new immunomodulatory effect of IL-27 on HIV-specific T cell function suggests its potential therapeutic use in cure strategies.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

About the journal

Abstract

Keywords