Host factors restricting the transmission of respiratory viruses are poorly characterized. We analyzed the contribution of type I and type III interferon (IFN) using a mouse model in which the virus is selectively administered to the upper airways, mimicking a natural respiratory virus infection. Mice lacking functional IFN-λ receptors (Ifnlr1−/−) no longer restricted virus dissemination from the upper airways to the lungs. Ifnlr1−/− mice shed significantly more infectious virus particles via the nostrils and transmitted the virus much more efficiently to naïve contacts compared with wild-type mice or mice lacking functional type I IFN receptors. Prophylactic treatment with IFN-α or IFN-λ inhibited initial virus replication in all parts of the respiratory tract, but only IFN-λ conferred long-lasting antiviral protection in the upper airways and blocked virus transmission. Thus, IFN-λ has a decisive and non-redundant function in the upper airways that greatly limits transmission of respiratory viruses to naïve contacts.
BackgroundInterleukin-37 (IL-37), a new member of IL-1 family cytokine, is recently identified as a natural inhibitor of innate immunity. This study aimed to measure the peripheral blood mononuclear cells (PBMCs) and serum levels of IL-37 in patients with systemic lupus erythematosus (SLE) and to investigate its role in SLE, including its correlation with disease activity, organ disorder and the regulation of inflammatory cytokines.MethodsThe expressions of IL-37 mRNAs in PBMCs and serum IL-37 levels in 66 SLE patients were measured by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). SLE patients PBMCs were stimulated with recombinant IL-37, levels of cytokines TNF-α, IL-1β, IL-6 and IL-10 were detected by RT-PCR and ELISA.ResultsIL-37 mRNAs and serum protein levels were higher in patients with SLE compared with healthy controls. Patients with active disease showed higher IL-37 mRNAs and serum protein levels compared with those with inactive disease as well as healthy controls. Serum IL-37 levels correlated with SLEDAI and inversely with C3 and C4. Serum IL-37 levels were higher in SLE patients with renal involvement compared with those without renal disease. In vitro, IL-37 inhibited the production of TNF-α, IL-1β and IL-6 in PBMCs of patients with SLE, whereas the production of IL-10 was unaffected.ConclusionsIL-37 associated with SLE disease activity, especially related with SLE renal disease activity. IL-37 is an important cytokine in the control of SLE pathogenesis by suppressing the production of inflammatory cytokines. Thus, IL-37 may provide a novel research target for the pathogenesis and therapy of SLE.
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