recombinant human interferon alfa-2a

Lost and found in translation: the value of the human imiquimod model.

Meijs Anouk C AC, van den Noort Juliette A JA, Assil Salma S, Klarenbeek Naomi B NB et al.

Topical imiquimod (IMQ), a Toll-like receptor (TLR) 7 agonist, induces transient cutaneous inflammation and is widely used in preclinical research as a 'psoriasis-like' mouse model. However, accumulating evidence indicates substantial divergence between IMQ-driven biology and human plaque psoriasis pathogenesis. To bridge this translational gap, we compare here the experimental conduct, readouts and mechanistic insights engaged by IMQ challenge in mice vs. healthy human participants. Importantly, molecular and cellular analyses indicate that IMQ predominantly activates interferon regulatory factor (IRF) signalling in humans, rather than NF-κB pathways as observed in animals. Moreover, differences in neutrophil response and complement activation were also identified. These discrepancies may reflect interspecies variation in TLR7 expression as well as methodological differences between the animal and human IMQ model. Despite certain limitations related to psoriasis translatability, the human IMQ model has demonstrated translational relevance in several early phase clinical trials. It represents a valuable tool for evaluating target engagement and characterizing downstream pharmacodynamic effects of novel compounds, particularly those targeting the TLR7-IRF-type I interferon axis. In conclusion, the human IMQ model can serve as valuable mechanistic model driving disease-related pathways, rather than as a proxy for plaque psoriasis disease biology. Fit-for-purpose benchmarking and method standardization are essential to maximize translational utility of the IMQ model.

Human vaccine responses regulated by parallel cytokine pathways.

Chen Guangbo G, Guo Jing J, Heath John J, Prestwood Tyler R TR et al.

Human vaccine responses vary widely, but the determinants remain incompletely defined. Here we analyzed 66 cytokines across four inactivated influenza vaccine (IIV) cohorts over five seasons (n = 581) and identified baseline serum interleukin (IL)-18 and interferon (IFN)-β as correlates of day 28 antibody responses. To test causality, we evaluated 19 cytokines in human tonsil and spleen organoids and found that type I IFNs, IL-21 and IL-12, but not IL-18 or IFNγ, enhanced antibody production. The addition of IFNβ to IIV recapitulated key features of the live-vaccine cytokine program. IL-12 and IL-21 defined a parallel pathway independent of type I IFNs, with IL-12 inducing IL-21 in humans, unlike in mice. Delivery of IL-21 or IFNβ via mRNA lipid nanoparticles in vivo promoted long-lived plasma cell formation. Together, these findings define parallel pathways that regulate vaccine immunity. Our approach unites high-throughput organoid testing and human cohort studies, establishing a human-centric platform to identify adjuvant candidates.

RETRACTION: PLK2 Phosphorylates and Inhibits Enriched TAp73 in Human Osteosarcoma Cells.

Z. B. Hu, X. H. Liao, Z. Y. Xu, X. Yang, C. Dong, A. M. Jin and H. Lu, "PLK2 Phosphorylates and Inhibits Enriched TAp73 in Human Osteosarcoma Cells," Cancer Medicine 5, no. 1 (2016): 74-87, https://doi.org/10.1002/cam4.558. The above article, published online on 02 December 2015 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Stephen Tait; and John Wiley and Sons Ltd. The retraction has been agreed upon following concerns raised by a third party. An investigation identified the duplication of bands within Figure 3F. Further duplications were observed between panels presented in Figure 8. An additional duplication was observed between the IB TAp73, 15 μg/mL Cis bands shown in Figure 2A and bands presented in another article published elsewhere by some of the same authors. In this case, the duplicate bands are shown to represent different proteins. The authors were contacted for their comments and supporting data but did not respond. The editors consider the results and conclusions to be compromised. The authors did not respond to our notice of retraction.

Correction: Deubiquitinase USP35 restrains STING-mediated interferon signaling in ovarian cancer.

Zhang Jiawen J, Chen Yunfei Y, Chen Xianfei X, Zhang Wen W et al.