IL-28B is a key regulator of B- and T-cell vaccine responses against influenza.

Autor: Adrian Egli, Deanna M Santer, Daire O'Shea, Khaled Barakat, Mohammedyaseen Syedbasha, Madeleine Vollmer, Aliyah Baluch, Rakesh Bhat, Jody Groenendyk, Michael A Joyce, Luiz F Lisboa, Brad S Thomas, Manuel Battegay, Nina Khanna, Thomas Mueller, D Lorne J Tyrrell, Michael Houghton, Atul Humar, Deepali Kumar
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: PLoS Pathogens, Vol 10, Iss 12, p e1004556 (2014)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1004556
Popis: Influenza is a major cause of morbidity and mortality in immunosuppressed persons, and vaccination often confers insufficient protection. IL-28B, a member of the interferon (IFN)-λ family, has variable expression due to single nucleotide polymorphisms (SNPs). While type-I IFNs are well known to modulate adaptive immunity, the impact of IL-28B on B- and T-cell vaccine responses is unclear. Here we demonstrate that the presence of the IL-28B TG/GG genotype (rs8099917, minor-allele) was associated with increased seroconversion following influenza vaccination (OR 1.99 p = 0.038). Also, influenza A (H1N1)-stimulated T- and B-cells from minor-allele carriers showed increased IL-4 production (4-fold) and HLA-DR expression, respectively. In vitro, recombinant IL-28B increased Th1-cytokines (e.g. IFN-γ), and suppressed Th2-cytokines (e.g. IL-4, IL-5, and IL-13), H1N1-stimulated B-cell proliferation (reduced 70%), and IgG-production (reduced>70%). Since IL-28B inhibited B-cell responses, we designed antagonistic peptides to block the IL-28 receptor α-subunit (IL28RA). In vitro, these peptides significantly suppressed binding of IFN-λs to IL28RA, increased H1N1-stimulated B-cell activation and IgG-production in samples from healthy volunteers (2-fold) and from transplant patients previously unresponsive to vaccination (1.4-fold). Together, these findings identify IL-28B as a key regulator of the Th1/Th2 balance during influenza vaccination. Blockade of IL28RA offers a novel strategy to augment vaccine responses.
Databáze: Directory of Open Access Journals
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