bims-hummad 2025-07-13 papers

Inflamm Bowel Dis. 2025 Jul 07. pii: izaf141. [Epub ahead of print]

Novel Autologous Regulatory T-Cell Therapy Ameliorates DSS-Induced Colitis in Humanized Mice.

Md Jabed Khan, Yoo Jin Lee, Su Yeon Lee, Hyeyeon Chung, Thuy Nguyen-Phuong, Yong-Hee Kim, Chung-Gyu Park, Young Mo Kang.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with a complex immune-mediated pathogenesis. The efficacy of human-specific cellular immunotherapies and biological medications cannot be accurately evaluated using traditional murine IBD models. Therefore, a humanized mouse model of IBD is necessary. Regulatory T cells (Tregs) are critical for maintaining intestinal immune homeostasis and may have therapeutic potential for treating IBD.
METHODS: Donor peripheral blood mononuclear cells (PBMCs) were used to reconstitute the human immune system in NOG mice and for Treg isolation. T cells were sorted and stimulated with anti-CD3 and anti-CD28 in the presence of irradiated feeder cells to prepare Treg cells. Two weeks after PBMC reconstitution in NOG mice, colitis was induced with dextran sodium sulfate (DSS). The expanded Treg cells were administered intravenously. Ozanimod was used as a positive control.
RESULTS: After expansion, 65.4% of the live CD4+ cells were Foxp3+CD25+ Treg cells and 14.5% were non-Treg cells. The mean human leukocyte (hCD45+) engraftment rate in the humanized mice was 56.5% ± 4.5%. Autologous Treg-cell therapy significantly reduced the disease activity index by 78% on day 7. Colonic length was preserved, and colonic inflammation was reduced in mice treated with Treg cells. Immunohistology revealed reduced human T-cell infiltration in Treg-treated mice.
CONCLUSIONS: Autologous Treg therapy ameliorated the symptoms of DSS-induced colitis in a humanized mouse model. The autologous PBMC-humanized DSS-induced colitis model may serve as a robust preclinical platform for evaluating the efficacy of personalized Treg cell therapy for IBD.

Keywords: autologous treg therapy; dextran sodium sulfate colitis; humanized mice; inflammatory bowel disease; preclinical model; regulatory T cells

DOI: https://doi.org/10.1093/ibd/izaf141

Sci Adv. 2025 Jul 11. 11(28): eadu1561

Establishment of a reverse genetics system for studying human immune functions in mice.

Priya Pal, Shuai Gao, Hongbo Gao, Xiwen Qin, Marina Cella, Qiankun Wang, Liang Shan.

Reverse genetics approaches in mice are widely used to understand gene functions and their aberrations in diseases. However, limitations exist in translating findings from animal models to human physiology. Humanized mice provide a powerful bridge to understanding human physiology and mechanisms of disease pathogenesis while maintaining the feasibility of working with small animals. Methods for generating humanized mouse models that allow scientists to probe contributions of particular genes have been rudimentary. Here, we established an efficient method for generating genetically modified human cord blood-derived CD34+ cells for transplantation, resulting in humanized mice with near-complete loss of specific gene expression by the human immune system. Mice transplanted with Cas9-edited human CD34+ cells recapitulate functional consequences of specific gene losses in the human immune system. Our approach enables targeted gene knockouts in humanized mice, offering a valuable tool for human gene function studies in vivo.

DOI: https://doi.org/10.1126/sciadv.adu1561

Clin Immunol. 2025 Jul 06. pii: S1521-6616(25)00134-2. [Epub ahead of print] 110559

Animal models of IgG4-related disease.

Manqi Tang, Weicheng Shen, Yanying Liu.

Immunoglobulin G4-Related Disease (IgG4-RD) is a recently characterized systemic autoimmune disorder marked by multiorgan inflammation and progressive fibrosis. It can affect nearly any organ and may lead to serious clinical consequences. Despite recent progress in developing animal models, therapeutic options for IgG4-RD remain limited, and the pathogenic mechanisms underlying immune dysregulation and fibrosis are still not fully understood. To support mechanistic and therapeutic research, both humanized and non-humanized animal models have been established in recent years. However, the unique biological features of the IgG4 molecule, together with genetic differences between humans and mice, present significant challenges to conventional mouse models. Although several models replicate certain features of IgG4-RD, none fully recapitulate the pathological hallmarks observed in patients. This review critically examines the strengths and limitations of current experimental models and outlines future directions for improving IgG4-RD model systems to better reflect human disease pathogenesis.

Keywords: Animal models; Humanized models; IgG4-RD; Non-humanized models

DOI: https://doi.org/10.1016/j.clim.2025.110559

Expert Opin Drug Discov. 2025 Jul 09. 1-16

Animal models of psoriasis for novel drug discovery: a literature update.

Zih-Chan Lin, Shih-Chun Yang, Thi Thu Phuong Tran, Jia-You Fang.

INTRODUCTION: Psoriasis is a chronic, immune-mediated inflammatory skin disorder with a multifactorial pathogenesis involving keratinocyte proliferation, dysregulated immune responses, and vascular remodeling. The development of effective therapeutics mainly relies on preclinical models that can reproduce disease-relevant mechanisms.
AREAS COVERED: This review outlines current in vivo psoriasis models, including spontaneous mutation models, transgenic and knockout mice, xenotransplantation systems, and cytokine-induced and imiquimod-induced models. Each model is evaluated for its ability to replicate key histological and immunological features of human psoriasis, such as acanthosis, immune cell infiltration, and cytokine network activation. The utility of CRISPR/Cas9 gene editing in generating targeted models is also discussed, thus highlighting its potential use for mechanistic studies. Finally, this review also emphasizes the limitations in translational applicability and the need for multimodel validation strategies regarding psoriasis. This article was based on a comprehensive literature search using PubMed, Scopus, and Google Scholar databases, covering publications from January 2015 to March 2025.
EXPERT OPINION: Despite extensive model development, no single system fully mimics human psoriatic disease. The imiquimod-induced model remains widely used due to its practicality, although it better reflects acute inflammation compared with chronic pathology. The combination of complementary models and the incorporation of human-derived tissues or immune components may improve translational relevance. Advances in genome editing and humanized systems are likely to shape the future of psoriasis research and therapeutic discovery.

Keywords: CRISPR/Cas9; Psoriasis; animal model; imiquimod; keratinocyte; xenograft

DOI: https://doi.org/10.1080/17460441.2025.2528959