bims-hummad Biomed News
on Humanised mouse models of autoimmune disorders
Issue of 2026–05–10
two papers selected by
Maksym V. Kopanitsa, Charles River Laboratories
  1. Double humanised lupus mouse model with human immune system and faecal microbiota from patients with SLE.
  2. Humanized immune system animal models and their recent applications.
  1. Lupus Sci Med. 2026 May 07. pii: e001982. [Epub ahead of print]13(1):
    Double humanised lupus mouse model with human immune system and faecal microbiota from patients with SLE.
    Tian Xu, Ran Lu, David N Oakland, Rana Estaleen, Amelia Rawlings, Hilary Montano, Santiago Diab, Jacquelyn S Michaelis, Mihai Pop, Adegbenga Bankole, Christopher M Reilly, Xin M Luo.
       OBJECTIVE: We aimed to create a double humanised lupus mouse model with a human immune system and faecal microbiota from patients with SLE.
    METHODS: We established the Double humanised SLE (DhuSLE) mouse by engrafting NSG immunodeficient mice with human CD34+ haematopoietic stem and progenitor cells (NSG-hu mice) and performing faecal microbiota transplantation from patients with SLE (SLE-FMT).
    RESULTS: While FMT in general transiently suppressed the development of human T cells in NSG-hu mice, SLE-FMT but not FMT from non-SLE donors promoted superficial skin lesions. Importantly, the combination of SLE-FMT and pristane in NSG-hu, now called the DhuSLE-P mouse, induced proteinuria although this clinical sign observed in mice did not reflect that of the microbiota donors. DhuSLE-P mice exhibited a higher level of human IgM in the circulation than NSG-hu mice, which was positively correlated with the frequency of plasma cells in the spleen. In the splenic sections of DhuSLE-P mice, nuclear BCL6 was minimally detected but CD138 expression was evident, suggesting that most plasma cells generated were not class switched and produced IgM. Some human IgG was detected in the kidney of DhuSLE-P mice with a trend towards increased total IgG in the serum. Analysis of the faecal microbiota revealed that the gut microbiota compositions were different between DhuSLE-P mice and NSG-hu mice due to SLE-FMT but not the injection of pristane.
    CONCLUSION: Together, these results introduced the first humanised lupus mouse model combining the human immune system and gut microbiota from patients with SLE. However, limitations exist and the model may benefit from methods that promote antibody class switching. On further development, the DhuSLE model can be useful for elucidating mechanisms and/or evaluating SLE treatments.
    Keywords:  Autoimmunity; Inflammation; Lupus Erythematosus, Systemic
    DOI:  https://doi.org/10.1136/lupus-2026-001982
  2. Animal Model Exp Med. 2026 May 06.
    Humanized immune system animal models and their recent applications.
    Nicolas Skuli, Rudra B Amin, A'ishah Bakayoko, Marisa Kruidenier, Sahara Aqui, Sarah J Skuli, Terence P Gade.
      Human or humanized immune system (HIS) animal models have emerged as indispensable tools for studying human biology and disease in vivo. By engrafting human hematopoietic and hematopoietic stem cells (HSC) into immunodeficient hosts, these models have enabled the development of a functional HIS, allowing the study of immune responses, disease mechanisms, and therapeutic interventions in a physiologically relevant setting. HIS models have broad applications across cancer research, infectious disease, regenerative medicine, and immunotherapy development. This review provides a comprehensive overview of the current landscape of HIS model generation, including HSC-based approaches, host strain selection, and recent advances involving genetically engineered mouse models expressing human cytokines and human leukocyte antigen molecules. We evaluated the strengths and limitations of these models, including issues with incomplete immune reconstitution and species-specific incompatibilities. We also discuss their increasing role in preclinical drug development and explore emerging innovations such as multitissue humanization and genome-editing strategies. As HIS models continue to evolve, they provide strong opportunities to bridge basic research and clinical translation.
    Keywords:  animal science; humanized mice; immunotherapy; patient‐derived xenografts; vaccines
    DOI:  https://doi.org/10.1002/ame2.70212
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