bims-hummad Biomed News
on Humanised mouse models of autoimmune disorders
Issue of 2025–09–28
two papers selected by
Maksym V. Kopanitsa, Charles River Laboratories
  1. Validation of a rheumatoid arthritis mouse model that uses NOD-scid IL2Rγnull mice reconstituted with patient PBMCs.
  2. Nanographene Oxide Attenuates Acute GVHD by Modulating Macrophage Polarization in a Xenogeneic Mouse Model.
  1. Dis Model Mech. 2025 Sep 22. pii: dmm.052294. [Epub ahead of print]
    Validation of a rheumatoid arthritis mouse model that uses NOD-scid IL2Rγnull mice reconstituted with patient PBMCs.
    Paula Schuster-Winkelmann, Veronika Weß, Marietta Schindler, Morten Ø Jensen, David E Shaw, Paolo Alberton, Hendrik Schulze-Koops, Silvia Schoenthaler, Andreas Weinhaeusel, Matthias Siebeck, Roswitha Gropp, Attila Aszodi.
      Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint destruction. Replicating human manifestations of RA in animal models remains challenging, however, due to heterogeneity of the disease. In this study, a humanized mouse model for RA was developed and validated using NOD-scid IL2Rnull (NSG) mice engrafted with peripheral blood mononuclear cells (PBMCs) from RA patients (NSG-RA). RA symptoms were induced using lipopolysaccharide and a cocktail of antibodies against type II collagen. Pathological manifestations were assessed through clinical scoring of hind paw swelling, histological analysis, and evaluation of RA-specific markers in plasma and joints using Luminex, RT-PCR, and RNA-seq. NSG-RA mice exhibited increased levels of RA-specific markers, an influx of inflammatory cells into the synovium, bone erosion, and elevated levels of human autoantibodies. Enriched RNA-seq pathway analysis revealed activation of the RA disease pathway, along with the TNF and IL-17 signaling pathways. Treatment with prednisolone or infliximab ameliorated disease symptoms and decreased levels of inflammatory markers. These findings indicate that the NSG-RA model offers a translational tool for studying RA pathogenesis and testing novel therapeutic approaches.
    Keywords:  Autoimmune disease; Humanized mouse model; Inflammatory markers; NOD-scid IL2Rynull (NSG) mice; Rheumatoid arthritis; Therapeutic evaluation
    DOI:  https://doi.org/10.1242/dmm.052294
  2. Adv Sci (Weinh). 2025 Sep 23. e04569
    Nanographene Oxide Attenuates Acute GVHD by Modulating Macrophage Polarization in a Xenogeneic Mouse Model.
    Aaron Yu, Hyun Sung Park, Dong-Hoon Chae, Jae Han Park, Jiyoung Heo, Keonwoo Cho, Jiho Kim, Hyewon Lee, Sueyeon Jee, Chanwoo Kim, Soon Won Choi, Jaechul Ryu, Eun-Hye Hur, Yunsuk Choi, Eun-Ji Choi, Mi-Kyung Oh, Hwa-Yong Lee, Je-Hwan Lee, Kyung-Rok Yu.
      Nanographene oxide (NGO) exhibits immunomodulatory activity and holds promise as a therapeutic agent for graft-versus-host disease (GVHD). In a xenogeneic GVHD mouse model, NGO administration improves survival and attenuates pathology with reduced weight loss and leukocyte engraftment, without sustained systemic toxicity. In GVHD patient-derived peripheral blood mononuclear cells (PBMCs), NGO treatment shifts T cell subsets toward immune homeostasis by increasing naïve T cells and decreasing effector memory T cells. Integrated transcriptomic analyses of PBMCs from GVHD patients and healthy donors reveal downregulation of pro-inflammatory and interferon-gamma-signal transducer and activator of transcription 1 (IFN-γ-STAT1)-associated genes, coinciding with the suppression of M1 macrophage signatures and induction of anti-inflammatory profiles. Mechanistically, NGO inhibits STAT1 activation and biases macrophages toward an anti-inflammatory state, independent of reactive oxygen species scavenging and lipopolysaccharide-myeloid differentiation primary response 88 (LPS-MyD88) signaling. To improve translational feasibility, NGO-primed macrophages (NGO-Mac) are generated, which produce higher levels of interleukin-10 (IL-10), inhibit helper T cell 1 (Th1) differentiation, and promote regulatory T cell (Treg) induction in an IL-10-dependent manner. In vivo, NGO-Mac therapy reduces M1 macrophage infiltration, increases Treg frequencies, and attenuates GVHD pathology. These findings highlight NGO and NGO-Mac as complementary immunotherapies, while further studies on safety, biodistribution, and feasibility are necessary for translation.
    Keywords:  graft versus host disease; humanized mouse; macrophage; nanographene oxide; nanomedicine
    DOI:  https://doi.org/10.1002/advs.202504569
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