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

doi:10.1016/j.isci.2021.103588

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

iScience. 2021 Dec 9;25(1):103588. doi: 10.1016/j.isci.2021.103588. eCollection 2022 Jan 21.

Authors

Jie Cheng¹, Timothy G Myers², Callie Levinger³, Princy Kumar⁴, Jai Kumar⁴, Bruktawit A Goshu^{1

5}, Alberto Bosque³, Marta Catalfamo¹

Affiliations

¹ Department of Microbiology and Immunology, Georgetown University School of Medicine, 3970 Reservoir Road, N.W, New Research Building, Room EG19A, Washington, DC 20057, USA.
² Genomic Technologies Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
³ Department of Microbiology, Immunology and Tropical Medicine, School of Medicine & Health Sciences, George Washington University, Washington, DC 20037, USA.
⁴ Division of Infectious Diseases and Travel Medicine, Georgetown University School of Medicine, Washington, DC 20057, USA.
⁵ Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

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

Keywords: Components of the immune system; Immune response; Transcriptomics.

Grants and funding

R01 AI145549/AI/NIAID NIH HHS/United States