IL-27 as effector molecule in viral infections and immunity

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Abstract

Interleukin-27 (IL-27) is a cytokine with multifaceted effects on immune responses. It is composed of two subunits: IL-27p28 и EBI3. The receptor complex for IL-27 consists of the heterodimeric IL-27R, which includes IL-27Rα and gp130. This receptor is expressed on various cell types, including T lymphocytes, B cells, NK cells, dendritic cells, macrophages, as well as endothelial and epithelial cells. Initially, IL-27 was primarily associated with Th1-mediated immune responses, but it is now recognized to also exhibit anti-inflammatory functions. IL-27 is mainly produced by antigen-presenting cells, such as dendritic cells and macrophages, but can also be secreted by adaptive immune cells. Its production is linked to infectious and autoimmune processes. The key effects of this cytokine include: direct modulation of effector CD4+ and CD8+ T-cell functions, stimulation of anti-inflammatory IL-10 production, recruitment of specialized regulatory T cells (Treg). In vitro, IL-27 promotes the proliferation of naïve CD4+ T lymphocytes through simultaneous binding to CD3 and the T-cell receptor. Additionally, this cytokine enhances CD4+ T-cell mobilization by increasing the secretion of chemokines and adhesion molecules. At the same time, IL-27 exerts anti-inflammatory effects, particularly by suppressing Th17-mediated immune responses. Despite its dual functionality, IL-27 is frequently associated with the progression of infectious processes in in vitro experiments and murine models. It serves as a crucial modulator of immune responses, capable of both activating protective mechanisms and restraining excessive inflammation. This study, based on literature data and the personal findings, highlights the diverse roles of IL-27 in viral infections such as influenza, HIV, COVID-19, and hepatitis B and C. The potential of IL-27 as a laboratory marker for clinical progression of viral infections remains to be fully elucidated. Its levels in peripheral blood are influenced by multiple factors, including the presence or absence of comorbidities. Thus, IL-27 is a key cytokine involved in the immunopathogenesis of viral infections. Investigating its diagnostic and differential significance in the aforementioned conditions may become a relevant scientific challenge.

About the authors

Zoya R. Korobova

St. Petersburg Pasteur Institute; Pavlov First St. Petersburg State Medical University

Author for correspondence.
Email: zoia-korobova@yandex.ru
ORCID iD: 0000-0003-0535-5014

PhD (Medicine), Junior Researcher, Laboratory of Molecular Immunology, Assistant Professor, Department of Immunology

Russian Federation, St. Petersburg; St. Petersburg

N. A. Arsentieva

St. Petersburg Pasteur Institute; Pavlov First St. Petersburg State Medical University

Email: arsentieva_n.a@bk.ru
ORCID iD: 0000-0003-2490-308X

PhD (Biology), Senior Researcher, Laboratory of Molecular Immunology, Associate Professor of the Department of Immunology

Russian Federation, St. Petersburg; St. Petersburg

A. A. Totolian

St. Petersburg Pasteur Institute; Pavlov First St. Petersburg State Medical University

Email: zoia-korobova@yandex.ru

RAS Full Member, DSc (Medicine), Professor, Director, Head of the Department of Immunology

Russian Federation, St. Petersburg; St. Petersburg

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