tetano
Editor, Senior Moderator
PLoS Pathog. 2014 Dec 11;10(12):e1004556. doi: 10.1371/journal.ppat.1004556. eCollection 2014.
[h=1]IL-28B is a Key Regulator of B- and T-Cell Vaccine Responses against Influenza.[/h] Egli A[SUP]1[/SUP], Santer DM[SUP]2[/SUP], O'Shea D[SUP]3[/SUP], Barakat K[SUP]4[/SUP], Syedbasha M[SUP]5[/SUP], Vollmer M[SUP]5[/SUP], Baluch A[SUP]6[/SUP], Bhat R[SUP]2[/SUP], Groenendyk J[SUP]7[/SUP], Joyce MA[SUP]2[/SUP], Lisboa LF[SUP]2[/SUP], Thomas BS[SUP]2[/SUP], Battegay M[SUP]8[/SUP], Khanna N[SUP]8[/SUP], Mueller T[SUP]9[/SUP], Tyrrell DL[SUP]2[/SUP], Houghton M[SUP]2[/SUP], Humar A[SUP]10[/SUP], Kumar D[SUP]10[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
PMID: 25503988 [PubMed - in process] Free full text
http://www.ncbi.nlm.nih.gov/pubmed/25503988
[h=1]IL-28B is a Key Regulator of B- and T-Cell Vaccine Responses against Influenza.[/h] Egli A[SUP]1[/SUP], Santer DM[SUP]2[/SUP], O'Shea D[SUP]3[/SUP], Barakat K[SUP]4[/SUP], Syedbasha M[SUP]5[/SUP], Vollmer M[SUP]5[/SUP], Baluch A[SUP]6[/SUP], Bhat R[SUP]2[/SUP], Groenendyk J[SUP]7[/SUP], Joyce MA[SUP]2[/SUP], Lisboa LF[SUP]2[/SUP], Thomas BS[SUP]2[/SUP], Battegay M[SUP]8[/SUP], Khanna N[SUP]8[/SUP], Mueller T[SUP]9[/SUP], Tyrrell DL[SUP]2[/SUP], Houghton M[SUP]2[/SUP], Humar A[SUP]10[/SUP], Kumar D[SUP]10[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
PMID: 25503988 [PubMed - in process] Free full text
http://www.ncbi.nlm.nih.gov/pubmed/25503988