Academic Journal
Homozygous IL37 mutation associated with infantile inflammatory bowel disease.
| العنوان: | Homozygous IL37 mutation associated with infantile inflammatory bowel disease. |
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| المؤلفون: | Zhang, Zinan Z, Zhang, Yu, He, Tingyan, Sweeney, Colin L, Baris, Safa, Karakoc-Aydiner, Elif, Yao, Yikun, Ertem, Deniz, Matthews, Helen F, Gonzaga-Jauregui, Claudia, Malech, Harry L, Su, Helen C, Ozen, Ahmet, Smith, Kenneth GC, Lenardo, Michael J |
| بيانات النشر: | Proceedings of the National Academy of Sciences Department of Medicine Student Department of Medicine //doi.org/10.1073/pnas.2009217118 Proc Natl Acad Sci U S A |
| سنة النشر: | 2023 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | IBD, IL37, VEO-IBD, immunodeficiency, inflammatory bowel disease, Child, Preschool, Female, Gene Expression Regulation, Humans, Induced Pluripotent Stem Cells, Inflammatory Bowel Diseases, Interleukin-1, Interleukin-18, Interleukin-1beta, Loss of Function Mutation, Macrophage Activation, Macrophages, Male |
| الوصف: | Interleukin (IL)-37, an antiinflammatory IL-1 family cytokine, is a key suppressor of innate immunity. IL-37 signaling requires the heterodimeric IL-18R1 and IL-1R8 receptor, which is abundantly expressed in the gastrointestinal tract. Here we report a 4-mo-old male from a consanguineous family with a homozygous loss-of-function IL37 mutation. The patient presented with persistent diarrhea and was found to have infantile inflammatory bowel disease (I-IBD). Patient cells showed increased intracellular IL-37 expression and increased proinflammatory cytokine production. In cell lines, mutant IL-37 was not stably expressed or properly secreted and was thus unable to functionally suppress proinflammatory cytokine expression. Furthermore, induced pluripotent stem cell-derived macrophages from the patient revealed an activated macrophage phenotype, which is more prone to lipopolysaccharide and IL-1β stimulation, resulting in hyperinflammatory tumor necrosis factor production. Insights from this patient will not only shed light on monogenic contributions of I-IBD but may also reveal the significance of the IL-18 and IL-37 axis in colonic homeostasis. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print; application/pdf |
| اللغة: | English |
| Relation: | https://www.repository.cam.ac.uk/handle/1810/347285 |
| DOI: | 10.17863/CAM.94700 |
| الاتاحة: | https://www.repository.cam.ac.uk/handle/1810/347285 https://doi.org/10.17863/CAM.94700 |
| Rights: | Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.8598DF9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.94700 |
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