title: TL1A regulates TCRγδ+ intraepithelial lymphocytes and gut microbial composition.
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 caecal Clostridial cluster IV, a change in the Firmicutes/Bacteroidetes ratio in caecum 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.
authors.affiliation: Department of Veterinary Disease Biology, Section of Experimental Animal Models, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Tougaard
authors.forename: S
authors.initials: S
authors.lastname: Skov
authors.forename: A E
authors.initials: AE
authors.lastname: Pedersen
authors.forename: L
authors.initials: L
authors.lastname: Krych
authors.forename: D S
authors.initials: DS
authors.lastname: Nielsen
authors.forename: M I
authors.initials: MI
authors.lastname: Bahl
authors.forename: E G
authors.initials: EG
authors.lastname: Christensen
authors.forename: T R
authors.initials: TR
authors.lastname: Licht
authors.forename: S S
authors.initials: SS
authors.lastname: Poulsen
authors.forename: S B
authors.initials: SB
authors.lastname: Metzdorff
authors.forename: A K
authors.initials: AK
authors.lastname: Hansen
authors.forename: C H F
authors.initials: CH
authors.lastname: Hansen
mesh_terms: D000273:Adipose Tissue / Q000276:immunology / Q000473:pathology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D054360:Chemokine CXCL1 / Q000235:genetics / Q000276:immunology; D003013:Clostridium / Q000276:immunology*; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D007778:Lactobacillus / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000235:genetics / Q000276:immunology*
chemical_list: D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016692:Receptors, Antigen, T-Cell, gamma-delta; C505947:Tnfsf15 protein, mouse; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15
keywords: Gut microbiota; Intraepithelial lymphocytes (IELs); NKG2D; TL1A; γδ T cells