E3 Ubiquitin Ligase NKLAM/RNF19b Regulates Inflammatory Cytokine Production in a Sendai Virus Pneumonia Model
JOURNAL OF IMMUNOLOGY(2019)
摘要
Abstract Recent studies have shown that E3 ubiquitin ligases are important mediators of the innate immune response. Studies from our laboratory have defined a role for the ubiquitin ligase natural killer lytic-associated molecule (NKLAM) in mouse and human innate immunity. Here, we present novel data describing a role for NKLAM in regulating the immune response to Sendai virus (SeV)-induced respiratory infection in mice. We found that NKLAM−/− mice demonstrated significantly less weight loss than wild type mice during SeV infection. Immunohistochemical analysis showed that the lungs of NKLAM−/− mice had less perivascular and peribronchial leukocyte accumulation than wild type mice. Using flow cytometry, we found the lungs of NKLAM−/− mice contained a lower percentage of neutrophils, macrophages and NK cells than wild type mice post-infection. The expression of several key pro-inflammatory cytokines/chemokines that are transcriptionally regulated by STAT1 and/or NFκB such as IL-6, IFNγ and MCP-1 was decreased in NKLAM−/− mice. Consistent with these findings, STAT1 and NFκB p65 phosphorylation were significantly lower in NKLAM−/− mice than in wild type mice. Collectively, our results suggest that NKLAM plays a role in orchestrating the innate immune response to SeV by regulating the expression of pro-inflammatory cytokines.
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