TNF Receptor 1 Promotes Early-Life Immunity and Protects against Colitis in Mice
| Autor: | Ying Huang, Jeffrey M. Bender, Philip E. Dubé, Shirin Nataneli, Fan Li, Cambrian Y. Liu, M. Kay Washington, Rabea Alhosh, D. Brent Polk, Shivesh Punit, Nandini Girish, Sharon S. Tam |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine microbiome Disease Inflammatory bowel disease antibiotics Mice 0302 clinical medicine Intestinal Mucosa mucosa lcsh:QH301-705.5 Subclinical infection Mice Knockout Dextran Sulfate respiratory system Colitis Interleukin-10 Receptors Tumor Necrosis Factor Type I Cytokines barrier Female Tumor necrosis factor alpha medicine.symptom Signal Transduction Colon IBD Inflammation Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Immune system Immunity medicine Animals Receptors Tumor Necrosis Factor Type II Tumor Necrosis Factor-alpha business.industry Epithelial Cells Inflammatory Bowel Diseases medicine.disease Mice Inbred C57BL 030104 developmental biology lcsh:Biology (General) Immunology Tumor Necrosis Factor Inhibitors weaning reaction business 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports, Vol 33, Iss 3, Pp 108275-(2020) Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY Neutralization of tumor necrosis factor (TNF) represents a widely used therapeutic strategy for autoimmune diseases including inflammatory bowel disease (IBD). However, the fact that many patients with IBD are non-responsive to anti-TNF therapies suggests the need for a better understanding of TNF signaling in IBD. Here, we show that co-deletion of TNF receptor 1 (TNFR1, Tnfrsf1a) in the Il10−/− spontaneous colitis model exacerbates disease, resulting in very-early-onset inflammation after weaning. The disease can be interrupted by treatment with antibiotics. The single deletion of TNFR1 induces subclinical colonic epithelial dysfunction and mucosal immune abnormalities, including accumulation of neutrophils and depletion of B cells. During the pre-disease period (before weaning), both Tnfr1−/− and Il10−/− Tnfr1−/− animals exhibit impaired expression of pro-inflammatory cytokines compared with wild-type and Il10−/− controls, respectively. Collectively, these results demonstrate the net anti-inflammatory functions of TNF/TNFR1 signaling through the regulation of colonic immune homeostasis in early life. Graphical Abstract In Brief Although anti-TNF therapies are used to treat colitis, Liu et al. demonstrate that colitis-susceptible mice deficient for TNF receptor 1 (TNFR1) paradoxically develop severe disease shortly after weaning. TNFR1 function can be traced back to its mediation of pro-inflammatory responses during a critical period of immune development in early life. |
| Databáze: | OpenAIRE |
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