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

Authors

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.
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.

Document Type

Journal Article

Publication Date

1-21-2022

Journal

iScience

Volume

25

Issue

1

DOI

10.1016/j.isci.2021.103588

Keywords

Components of the immune system; Immune response; Transcriptomics

Abstract

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 TIGITHIV-specific T cells. This new immunomodulatory effect of IL-27 on HIV-specific T cell function suggests its potential therapeutic use in cure strategies.

APA Citation

Cheng, Jie; Myers, Timothy G.; Levinger, Callie; Kumar, Princy; Kumar, Jai; Goshu, Bruktawit A.; Bosque, Alberto; and Catalfamo, Marta, "IL-27 induces IFN/STAT1-dependent genes and enhances function of TIGIT HIVGag-specific T cells" (2022). GW Authored Works. Paper 499.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/499

Department

Microbiology, Immunology, and Tropical Medicine