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Unique IL-13R?2/STAT3 mediated IL-13 regulation detected in lung conventional dendritic cells, 24?h post viral vector vaccination.


ABSTRACT: This study demonstrates that 24?h following viral vector-based vaccination IL-13R?2 functions as a master sensor on conventional dendritic cells (cDCs), abetted by high protein stability coupled with minimal mRNA expression, to rapidly regulate DC mediated IL-13 responses at the lung mucosae, unlike IL-13R?1. Under low IL-13, IL-13R?2 performs as a primary signalling receptor, whilst under high IL-13, acts to sequester IL-13 to maintain homeostasis, both in a STAT3-dependent manner. Likewise, we show that viral vector-derived IL-13 levels at the vaccination site can induce differential STAT3/STAT6 paradigms in lung cDC, that can get regulated collaboratively or independently by TGF-?1 and IFN-?. Specifically, low IL-13 responses associated with recombinant Fowlpox virus (rFPV) is regulated by early IL-13R?2, correlated with STAT3/TGF-?1 expression. Whilst, high IL-13 responses, associated with recombinant Modified Vaccinia Ankara (rMVA) is regulated in an IL-13R?1/STAT6 dependent manner associated with IFN-?R expression bias. Different viral vaccine vectors have previously been shown to induce unique adaptive immune outcomes. Taken together current observations suggest that IL-13R?2-driven STAT3/STAT6 equilibrium at the cDC level may play an important role in governing the efficacy of vector-based vaccines. These new insights have high potential to be exploited to improve recombinant viral vector-based vaccine design, according to the pathogen of interest and/or therapies against IL-13 associated disease conditions.

SUBMITTER: Roy S 

PROVIDER: S-EPMC6978450 | BioStudies | 2020-01-01

REPOSITORIES: biostudies

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