Abstract
An animal model for autoinflammation with infantile enterocolitis reveals novel therapeutic strategies 2554
The Journal of immunology (1950), Vol.214(Supplement_1), vkaf283460
11/01/2025
DOI: 10.1093/jimmun/vkaf283.460
Abstract
Abstract Description
Autoinflammation with infantile enterocolitis (AIFEC) is a severe, emerging disorder caused by inborn errors in the NLRC4 gene. Due to the lack of suitable animal models, no standard therapy currently exists for AIFEC. To address this gap, we have developed a loxP-flanked NLRC4 V341A conditional knock-in (KI) mouse model that recapitulates AIFEC-like symptoms, including 100% mortality in KI pups within 10 days of birth. Using this novel model, we evaluated potential therapies by administering treatments from postnatal days 1 to 7, with daily monitoring to adulthood. Colitis was assessed by colon histology, diarrhea, and pro-inflammatory gene expression; while autoinflammation was evaluated by serum ferritin, IL-1β, IL-18, and hemophagocytosis on days 8 and 22. IL18BP, a treatment previously used in AIFEC patients, improved survival to 80%, alleviated colitis and autoinflammation by day 8, and increased body weight to 65.6% of wild-type controls by day 22. Given AIFEC’s relation to very early-onset IBD, we also tested TNF blockade, which raised survival to 90%, with dramatic reduced colitis and autoinflammation by day 8, and increased body weight to 70.7% of wild-type by day 22. Interestingly, KI pups also exhibited hypoglycemia, with glucose supplementation showing therapeutic benefits. In all cases, two weeks post-treatments, only mild inflammation remained. All surviving KI pups reached adulthood. These findings suggest promising treatment avenues for AIFEC.
Funding Sources
Startup fund from the Department of pathology at the University of IOWA.
Topic Categories
Basic Autoimmunity (BA)
Details
- Title: Subtitle
- An animal model for autoinflammation with infantile enterocolitis reveals novel therapeutic strategies 2554
- Creators
- Yuhang Wang - University of IowaJoyce Gao - University of IowaYiqin Xiong - University of IowaZizhen Kang - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.214(Supplement_1), vkaf283460
- DOI
- 10.1093/jimmun/vkaf283.460
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- Oxford University Press
- Grant note
- Department of pathology at the University of IOWA
Startup fund from the Department of pathology at the University of IOWA.
- Alternative title
- IMMUNOLOGY2025™ Abstracts
- Language
- English
- Date published
- 11/01/2025
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Surgery
- Record Identifier
- 9985035030402771
Metrics
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