| First Author | Roy S | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 1017 |
| PubMed ID | 31974500 | Mgi Jnum | J:297753 |
| Mgi Id | MGI:6479224 | Doi | 10.1038/s41598-020-57815-z |
| Citation | Roy S, et al. (2020) Unique IL-13Ralpha2/STAT3 mediated IL-13 regulation detected in lung conventional dendritic cells, 24 h post viral vector vaccination. Sci Rep 10(1):1017 |
| abstractText | This study demonstrates that 24 h following viral vector-based vaccination IL-13Ralpha2 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-13Ralpha1. Under low IL-13, IL-13Ralpha2 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-beta1 and IFN-gamma. Specifically, low IL-13 responses associated with recombinant Fowlpox virus (rFPV) is regulated by early IL-13Ralpha2, correlated with STAT3/TGF-beta1 expression. Whilst, high IL-13 responses, associated with recombinant Modified Vaccinia Ankara (rMVA) is regulated in an IL-13Ralpha1/STAT6 dependent manner associated with IFN-gammaR expression bias. Different viral vaccine vectors have previously been shown to induce unique adaptive immune outcomes. Taken together current observations suggest that IL-13Ralpha2-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. |
