2021-03-01·Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology
[Tolerogenic dendritic cells alleviate joint inflammation and arthropathy via reducing Th1 and Th17 cell proportion in CIA rats].
作者: Guilan Ma ; Yan Tan ; Yaling Tian ; Lunmin Bao ; Hongmei Jiang
Objective To investigate the effects of tolerogenic dendritic cells (tolDCs) induced by nuclear factor κB oligodeoxynucleotide decoy (NF-κB ODN decoy) on Th1 cells, Th2 cells, Th17 cells and regulatory T cells (Tregs) and the intervention effects on collagen-induced arthritis (CIA) rats. Methods SD female rats used to establish CIA rat models were divided into four groups, including a CIA model group, a bovine type II collagen-decoy-dendritic cell (Col2-decoy DC) treatment group, a blank control group, and a Col2-decoy DC control group. On the 20th days after the first immunization, the rats were injected with tolDCs via the tail vein, and the rats were sacrificed on the 7th weeks. The proportions of Th1 cells, Th2 cells, Th17 cells, and Tregs in the rat spleen were detected by flow cytometry. The ankle joint pathomorphological change was evaluated by HE staining, and the arthritis index (AI) was scored. Results Compared with the CIA model group, the Col2-decoy DC group had lower AI and milder ankle joint pathomorphological change. The percentages of Th1 cells and Th17 cells in the spleen CD4+ T cells decreased, while the percentages of Th2 cells and Tregs increased. Conclusion The treatment of tolDCs can alleviate the inflammation and arthropathy of CIA rats by reducing the proportion of Th1 and Th17 cells in CD4+ T cells.
Multivalent IgM scaffold enhances the therapeutic potential of variant-agnostic ACE2 decoys against SARS-CoV-2.
作者: Meghan M Verstraete ; Florian Heinkel ; Janessa Li ; Siran Cao ; Anh Tran ; Elizabeth C Halverson ; Robert Gene ; Elizabeth Stangle ; Begonia Silva-Moreno ; Sifa Arrafi ; Jegarubee Bavananthasivam ; Madeline Fung ; Mariam Eji-Lasisi ; Stephanie Masterman ; Steve Xanthoudakis ; Surjit Dixit ; John Babcook ; Brandon Clavette ; Mark Fogg ; Eric Escobar-Cabrera
As immunological selection for escape mutants continues to give rise to future SARS-CoV-2 variants, novel universal therapeutic strategies against ACE2-dependent viruses are needed. Here we present an IgM-based decavalent ACE2 decoy that has variant-agnostic efficacy. In immuno-, pseudovirus, and live virus assays, IgM ACE2 decoy had potency comparable or superior to leading SARS-CoV-2 IgG-based mAb therapeutics evaluated in the clinic, which were variant-sensitive in their potency. We found that increased ACE2 valency translated into increased apparent affinity for spike protein and superior potency in biological assays when decavalent IgM ACE2 was compared to tetravalent, bivalent, and monovalent ACE2 decoys. Furthermore, a single intranasal dose of IgM ACE2 decoy at 1 mg/kg conferred therapeutic benefit against SARS-CoV-2 Delta variant infection in a hamster model. Taken together, this engineered IgM ACE2 decoy represents a SARS-CoV-2 variant-agnostic therapeutic that leverages avidity to drive enhanced target binding, viral neutralization, and in vivo respiratory protection against SARS-CoV-2.