title: Innate interferons inhibit allergen and microbial specific T(H)2 responses.
abstract: Several studies provided evidence of innate interferons (IFNs) regulating T(H)2 cytokine production using purified CD4(+) memory cells and T(H)2 polarisation via interleukin-4 (IL-4). Vitally, none of these previous studies examined IFN attenuation of T(H)2 responses to allergen or antigen. This study therefore sought to investigate the abrogation of specific allergen- and antigen-stimulated T(H)2 response in peripheral blood mononuclear cells (PBMC) derived from 12 sensitised individuals by IFN-β and IFN-λ. PBMC were cultured in the presence of house dust mite (HDM) allergen, rhinovirus (RV), influenza vaccine and tetanus toxoid (TT)±either IFN-β or IFN-λ for 3 and 5 days. IFN-γ, IL-5 and IL-13 protein levels were measured by ELISA. Quantitative PCR (qPCR) was used to investigate induction of genes involved in control of T(H)2 cytokines. No alteration in T(H)1 IFN-γ allergen/antigen response was observed with addition of IFN-β or IFN-λ. Consistent abrogation of T(H)2 response to HDM and influenza was observed with IFN-β at both time points; attenuation was observed by day 5 with RV and TT. IFN-λ had no consistent effect on T(H)2 production except in the presence of RV (multiplicity of infection=5); a decrease in IL-5 alone was observed in the presence of trivalent inactivated influenza vaccine. GATA binding protein 3 (GATA3) and suppressors of cytokine signalling3 mRNA were differentially regulated in HDM and influenza-stimulated cultures±IFN-β. We concluded that IFN-β produced a strong and consistent abrogation of T(H)2 cytokine production in the presence of a range of allergen and antigen stimulants.
authors: Lung and Allergy Research Centre, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Buranda, Brisbane, Australia. a.pritchard2@uq.edu.au
authors: Antonia L
authors: AL
authors: Pritchard
authors: Olivia J
authors: OJ
authors: White
authors: Julie G
authors: JG
authors: Burel
authors: John W
authors: JW
authors: Upham
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology; D039741:Antigens, Dermatophagoides / Q000276:immunology; D002478:Cells, Cultured; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects; D007114:Immunization; D007252:Influenza Vaccines / Q000276:immunology; D016899:Interferon-beta / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D012229:Rhinovirus / Q000276:immunology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D013744:Tetanus Toxin / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D000095022:Interferon Lambda
chemical_list: D000942:Antigens, Bacterial; D039741:Antigens, Dermatophagoides; D050990:GATA3 Transcription Factor; D007252:Influenza Vaccines; D016899:Interferon-beta; D007378:Interleukins; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013744:Tetanus Toxin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C106644:SOCS3 protein, human