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In this study, recombinant pox viral vaccination was shown to induce highly elevated IgG2a and low IgG1 antibody expression in mice lacking IL-4 or STAT6, whilst IL-13-/- mice exhibited elevated IgG1, but very low IgG2a. These findings revealed that IL-13 and IL-4 differentially regulated antibody development. To understand this further, when STAT6-/- mice were given a vaccine co-expressing IL-13Rα2 that temporarily sequestered IL-13, significantly reduced IgG2a expression, was detected. These findings for the first time demonstrated that IL-13 regulated IgG2a differentiation utilising an alternative IL-13R signalling pathway independent of STAT6 (IL-13Rα2 pathway). This was further corroborated by the (i) elevated IL-13Rα2 expression detected on STAT6-/- lung MHCII+ CD11c+ cells 24 h post IL-13 inhibitor vaccination and ii) significant up-regulation of IL-13Rα2 expression on spleen and lung derived MHCII+ CD11c+ following inhibition of STAT6 signalling in vitro, or vaccination with IL-4R/STAT6 antagonist in vivo. When T follicular helper (Tfh) cells which regulate antibody differentiation were assessed post vaccination, although no difference in IL-4 expression was observed, greatly reduced IFN-γ expression was detected in IL-13-/- and STAT6-/- mice compared to wild-type. These findings support the notion that the balance of IL-13 level at the vaccination site can differentially regulate T and B-cell immune outcomes.

Original publication

DOI

10.1002/eji.201747463

Type

Journal article

Journal

Eur J Immunol

Publication Date

07/2018

Volume

48

Pages

1153 - 1163

Keywords

Antibody differentiation, IL-13, IL-13Rα2, STAT6, Tfh, Animals, Antibodies, Viral, Avipoxvirus, Cells, Cultured, Immunoglobulin Class Switching, Immunoglobulin G, Immunoglobulin Isotypes, Interleukin-13, Interleukin-13 Receptor alpha2 Subunit, Interleukin-4, Mice, Mice, Inbred C57BL, Mice, Knockout, Poxviridae Infections, STAT6 Transcription Factor, Signal Transduction, T-Lymphocytes, Helper-Inducer, Viral Vaccines