دورية أكاديمية
TNF overproduction impairs epithelial staphylococcal response in hyper IgE syndrome.
| العنوان: | TNF overproduction impairs epithelial staphylococcal response in hyper IgE syndrome. |
|---|---|
| المؤلفون: | Myles, Ian A, Anderson, Erik D, Earland, Noah J, Zarember, Kol A, Sastalla, Inka, Williams, Kelli W, Gough, Portia, Moore, Ian N, Ganesan, Sundar, Fowler, Cedar J, Laurence, Arian, Garofalo, Mary, Kuhns, Douglas B, Kieh, Mark D, Saleem, Arhum, Welch, Pamela A, Darnell, Dirk A, Gallin, John I, Freeman, Alexandra F, Holland, Steven M, Datta, Sandip K |
| المصدر: | J Clin Invest ; ISSN:1558-8238 ; Volume:128 ; Issue:8 |
| بيانات النشر: | American Society for Clinical Investigation |
| سنة النشر: | 2018 |
| المجموعة: | PubMed Central (PMC) |
| مصطلحات موضوعية: | Immunology, Immunotherapy, Infectious disease |
| الوصف: | Autosomal dominant hyper IgE syndrome (AD-HIES), or Job's syndrome, is a primary immune deficiency caused by dominant-negative mutations in STAT3. Recurrent Staphylococcus aureus skin abscesses are a defining feature of this syndrome. A widely held hypothesis that defects in peripheral Th17 differentiation confer this susceptibility has never been directly evaluated. To assess the cutaneous immune response in AD-HIES, we induced suction blisters in healthy volunteers (HVs) and patients with AD-HIES and then challenged the wound with lethally irradiated bacteria. We show that cutaneous production of IL-17A and IL-17F was normal in patients with AD-HIES. Overproduction of TNF-α differentiated the responses in AD-HIES from HVs. This was associated with reduced IL-10 family signaling in blister-infiltrating cells and defective epithelial cell function. Mouse models of AD-HIES recapitulated these aberrant epithelial responses to S. aureus and involved defective epithelial-to-mesenchymal transition (EMT) rather than a failure of bacterial killing. Defective responses in mouse models of AD-HIES and primary keratinocyte cultures from patients with AD-HIES could be reversed by TNF-α blockade and by drugs with reported modulatory effects on EMT. Our results identify these as potential therapeutic approaches in patients with AD-HIES suffering S. aureus infections. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1172/JCI121486Test; https://pubmed.ncbi.nlm.nih.gov/30035749Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063472Test/ |
| DOI: | 10.1172/JCI121486 |
| الإتاحة: | https://doi.org/10.1172/JCI121486Test https://pubmed.ncbi.nlm.nih.gov/30035749Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063472Test/ |
| رقم الانضمام: | edsbas.A71F8B20 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1172/JCI121486 |
|---|