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IL-13Rα2 Regulates the IL-13/IFN-γ Balance during Innate Lymphoid Cell and Dendritic Cell Responses to Pox Viral
Zheyi Li1, Sreeja Roy1,2, Charani Ranasinghe1
1Molecular Mucosal Vaccine Immunology Group, Department of Immunology and infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia.
Vaccines
|June 2, 2021
Summary
Manipulating interleukin-13 (IL-13) and STAT6 signaling during vaccination impacts innate lymphoid cell (ILC) and dendritic cell (DC) interactions. This influences T cell function and antibody production, crucial for effective vaccine design.
Area of Science:
- Immunology
- Vaccinology
Background:
- Interleukin-13 (IL-13) and STAT6 signaling are critical in immune responses at vaccination sites.
- Innate lymphoid cells (ILCs) and dendritic cells (DCs) play key roles in shaping adaptive immunity.
- Previous work demonstrated that modulating IL-13 and STAT6 affects ILC/DC recruitment and T cell responses.
Purpose of the Study:
- To investigate the distinct effects of permanent versus transient blockage of IL-13 and STAT6 signaling on ILC subsets and their cytokine production.
- To explore the regulation of IL-13 receptor alpha 2 (IL-13Rα2) and IL-4 receptors on ILCs under different STAT6 inhibition conditions.
- To elucidate the role of IL-13 as a master regulator of ILCs and DCs in viral vector vaccination and its impact on adaptive immunity.
Main Methods:
- Utilized STAT6-deficient (STAT6-/-) BALB/c mice and wild-type BALB/c mice.
- Administered fowl pox virus (FPV) expressing HIV antigens.
- Employed FPV-HIV with an IL-4 receptor antagonist for transient STAT6 inhibition.
- Analyzed ILC-derived IL-13 and interferon-gamma (IFN-γ) profiles.
- Assessed IL-13Rα2 and IL-4 receptor expression on ILCs and DCs.
- Examined lung mucosal immune responses 24 hours post-vaccination.
Main Results:
- Permanent STAT6 blockage in STAT6-/- mice led to increased ILC2-derived IL-13 and decreased ILC1/ILC3-derived IFN-γ.
- Transient STAT6 inhibition resulted in decreased IL-13 and increased IFN-γ.
- STAT6 signaling disruption significantly impacted IL-13Rα2 expression on ILC2 and ILC1/ILC3 subsets.
- Evidence suggested autocrine regulation of IL-13 and IL-13Rα2 by lung ILC2.
- Inter-regulation between lung ILC2-derived IL-13 and ILC1/ILC3-derived IFN-γ was proposed via their respective receptors.
- Differential regulation of IL-13/IL-13Rα2 on lung DCs was observed under varying IL-13 conditions.
Conclusions:
- IL-13 acts as a master regulator for both DCs and ILC subsets during early viral vector vaccination.
- STAT6 signaling profoundly influences IL-13 production and receptor expression on ILCs.
- Targeting IL-13Rα2 and STAT6 signaling in ILCs/DCs offers a promising strategy for developing more effective vaccines against various pathogens.
