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TNF Receptor 1 Promotes Early-Life Immunity and Protects Against Colitis in Mice

Overview
Journal Cell Rep
Publisher Cell Press
Date 2020 Oct 21
PMID 33086075
Citations 11
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Abstract

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 Il10Tnfr1 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.

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References
1.
McGovern D, Kugathasan S, Cho J . Genetics of Inflammatory Bowel Diseases. Gastroenterology. 2015; 149(5):1163-1176.e2. PMC: 4915781. DOI: 10.1053/j.gastro.2015.08.001. View

2.
Salzer E, Kansu A, Sic H, Majek P, Ikinciogullari A, Dogu F . Early-onset inflammatory bowel disease and common variable immunodeficiency-like disease caused by IL-21 deficiency. J Allergy Clin Immunol. 2014; 133(6):1651-9.e12. DOI: 10.1016/j.jaci.2014.02.034. View

3.
Wang K, Han G, Dou Y, Wang Y, Liu G, Wang R . Opposite role of tumor necrosis factor receptors in dextran sulfate sodium-induced colitis in mice. PLoS One. 2013; 7(12):e52924. PMC: 3532169. DOI: 10.1371/journal.pone.0052924. View

4.
Korzenik J, Larsen M, Nielsen J, Kjeldsen J, Norgard B . Increased risk of developing Crohn's disease or ulcerative colitis in 17 018 patients while under treatment with anti-TNFα agents, particularly etanercept, for autoimmune diseases other than inflammatory bowel disease. Aliment Pharmacol Ther. 2019; 50(3):289-294. DOI: 10.1111/apt.15370. View

5.
Bianco A, Girardelli M, Tommasini A . Genetics of inflammatory bowel disease from multifactorial to monogenic forms. World J Gastroenterol. 2015; 21(43):12296-310. PMC: 4649114. DOI: 10.3748/wjg.v21.i43.12296. View