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IL-28B is a Key Regulator of B- and T-Cell Vaccine Responses against Influenza
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نویسنده
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egli a. ,santer d.m. ,o'shea d. ,barakat k. ,syedbasha m. ,vollmer m. ,baluch a. ,bhat r. ,groenendyk j. ,joyce m.a. ,lisboa l.f. ,thomas b.s. ,battegay m. ,khanna n. ,mueller t. ,tyrrell d.l.j. ,houghton m. ,humar a. ,kumar d.
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منبع
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plos pathogens - 2014 - دوره : 10 - شماره : 12
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چکیده
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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. © 2014 egli et al.
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آدرس
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infection biology,department of biomedicine,university of basel,basel,switzerland,li ka shing institute of virology,university of alberta,edmonton,ab, Canada, li ka shing institute of virology,university of alberta,edmonton,ab, Canada, li ka shing institute of virology,university of alberta,edmonton,ab,canada,division of infectious diseases,university of alberta,edmonton,ab, Canada, li ka shing institute of virology,university of alberta,edmonton,ab,canada,university of alberta, Canada, infection biology,department of biomedicine,university of basel,basel, Switzerland, infection biology,department of biomedicine,university of basel,basel, Switzerland, division of infectious diseases,moffitt cancer center,tampa,fl, United States, li ka shing institute of virology,university of alberta,edmonton,ab, Canada, department of biochemistry,school of translational medicine,university of alberta,edmonton,ab, Canada, li ka shing institute of virology,university of alberta,edmonton,ab, Canada, li ka shing institute of virology,university of alberta,edmonton,ab, Canada, li ka shing institute of virology,university of alberta,edmonton,ab, Canada, infection biology,department of biomedicine,university of basel,basel,switzerland,division of infectious diseases and hospital epidemiology,university hospital of basel, Switzerland, infection biology,department of biomedicine,university of basel,basel,switzerland,division of infectious diseases and hospital epidemiology,university hospital of basel, Switzerland, division of nephrology,university hospital of zurich,zurich, Switzerland, li ka shing institute of virology,university of alberta,edmonton,ab, Canada, li ka shing institute of virology,university of alberta,edmonton,ab, Canada, department of medicine and multi-organ transplant program,university health network,toronto,on, Canada, department of medicine and multi-organ transplant program,university health network,toronto,on, Canada
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Authors
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