TL1A regulates TCRγδ+ intraepithelial lymphocytes and gut microbial composition
P. Tougaard1*, S. Skov1, A.E. Pedersen2, L. Krych3, D.S. Nielsen3, M.I. Bahl4, E.G. Christensen4, T.R. Licht4, S.S. Poulsen5, S.B. Metzdorff1, A.K. Hansen1, C.H.F. Hansen1
1Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
2Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
3Department of Food Science, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
4National Food Institute, Division of Microbiology and Risk Assessment, Technical University of Denmark, Moerkhøj, Denmark
5Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Abstract
TL1A is a proinflammatory cytokine, which is prevalent in the gut. High TL1A concentrations are present in patients with inflammatory bowel disease (IBD), and in IBD mouse models. However, the role of TL1A during steady state conditions is relatively unknown. Here, we used TL1A knockout (KO) mice to analyse the impact of TL1A on the intestinal immune system and gut microbiota. The TL1A KO mice showed reduced amounts of small intestinal intraepithelial TCRγδ+ and CD8+ T cells, and reduced expression of the activating receptor NKG2D. Moreover, the TL1A KO mice had significantly reduced body weight and visceral adipose tissue deposits, as well as lower levels of leptin and CXCL1, compared with wild-type mice. Analysis of the gut microbial composition of TL1A KO mice revealed a reduction of cecal Clostridial cluster IV, a change in the Firmicutes/Bacteroidetes ratio in cecum, and less Lactobacillus spp. in the mucosal ileum. Our results show that TL1A deficiency impacts on the gut microbial composition and the mucosal immune system, especially the intraepithelial TCRγδ+ T cell subset, and that TL1A is involved in the establishment of adipose tissue. This research contributes to a broader understanding of TL1A inhibition, which is increasingly considered for treatment of IBD.
European Journal of Immunology