ArticleCellular and molecular gastroenterology and hepatology2020
Elucidation of the Effects of a Current X-SCID Therapy on Intestinal Lymphoid Organogenesis Using an In Vivo Animal Model.
Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- Primary Immunodeficiencies Associated With Early-Onset Inflammatory Bowel Disease in Southeast and East Asia.Frontiers in immunology · 2021Pooled it
- Long-term engraftment of human stem and progenitor cells for large-scale production of functional immune cells in engineered pigs.Nature biomedical engineering · 2025Article
- Alternatives to antibiotics in pig production: looking through the lens of immunophysiology.Stress biology · 2024Review
- Development of a rational framework for the therapeutic efficacy of fecal microbiota transplantation for calf diarrhea treatment.Microbiome · 2022Article
- Organogenesis of Ileal Peyer's Patches Is Initiated Prenatally and Accelerated Postnatally With Comprehensive Proliferation of B Cells in Pigs.Frontiers in immunology · 2020Article
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Authors and funding
20 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsOrgan-level research using an animal model lacking Il2rg, the gene responsible for X-linked severe combined immunodeficiency (X-SCID), is clinically unavailable and would be a powerful tool to gain deeper insights into the symptoms of patients with X-SCID.
methodsWe used an X-SCID animal model, which was first established in our group by the deletion of Il2rg gene in pigs, to understand the clinical signs from multiple perspectives based on pathology, immunology, microbiology, and nutrition. We also treated the X-SCID pigs with bone marrow transplantation (BMT) for mimicking a current therapeutic treatment for patients with X-SCID and investigated the effect at the organ-level. Moreover, the results were confirmed using serum and fecal samples collected from patients with X-SCID.
resultsWe demonstrated that X-SCID pigs completely lacked Peyer's patches (PPs) and IgA production in the small intestine, but possessed some dysfunctional intestinal T and B cells. Another novel discovery was that X-SCID pigs developed a heterogeneous intestinal microflora and possessed abnormal plasma metabolites, indicating that X-SCID could be an immune disorder that affects various in vivo functions. Importantly, the organogenesis of PPs in X-SCID pigs was not promoted by BMT. Although a few isolated lymphoid follicles developed in the small intestine of BMT-treated X-SCID pigs, there was no evidence that they contributed to IgA production and microflora formation. Consistently, most patients with X-SCID who received BMT possessed abnormal intestinal immune and microbial environments regardless of the presence of sufficient serum IgG.
conclusionsThese results indicate that the current BMT therapies for patients with X-SCID may be insufficient to induce the organogenesis of intestinal lymphoid tissues that are associated with numerous functions in vivo.
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