TL1A regulates TCRγδ+ intraepithelial lymphocytes and gut microbial composition

Peter Tougaard; Søren Skov; Anders Elm Pedersen; Lukasz Krych; Dennis Sandris Nielsen; Martin Iain Bahl; E.G. Christensen; Tine Rask Licht; Steen Seier Poulsen; Stine Broeng Metzdorff; Axel Kornerup Hansen; Camilla Hartmann Friis Hansen

doi:10.1002/eji.201444528

TL1A regulates TCRγδ⁺ intraepithelial lymphocytes and gut microbial composition

Peter Tougaard, Søren Skov, Anders Elm Pedersen, Lukasz Krych, Dennis Sandris Nielsen, Martin Iain Bahl, E.G. Christensen, Tine Rask Licht, Steen Seier Poulsen, Stine Broeng Metzdorff, Axel Kornerup Hansen, Camilla Hartmann Friis Hansen

16 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	European Journal of Immunology
Vol/bind	45
Udgave nummer	3
Sider (fra-til)	865-875
Antal sider	11
ISSN	0014-2980
DOI	https://doi.org/10.1002/eji.201444528
Status	Udgivet - 1 mar. 2015

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Citationsformater

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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.",

keywords = "Faculty of Health and Medical Sciences, γδ T cells, Gut microbiota, Intraepithelial lymphocytes (IELs), NKG2D, TL1A",

author = "Peter Tougaard and S{\o}ren Skov and Pedersen, {Anders Elm} and Lukasz Krych and Nielsen, {Dennis Sandris} and Bahl, {Martin Iain} and E.G. Christensen and Licht, {Tine Rask} and Poulsen, {Steen Seier} and Metzdorff, {Stine Broeng} and Hansen, {Axel Kornerup} and Hansen, {Camilla Hartmann Friis}",

note = "{\textcopyright} 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",

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TY - JOUR

T1 - TL1A regulates TCRγδ+ intraepithelial lymphocytes and gut microbial composition

AU - Tougaard, Peter

AU - Skov, Søren

AU - Pedersen, Anders Elm

AU - Krych, Lukasz

AU - Nielsen, Dennis Sandris

AU - Bahl, Martin Iain

AU - Christensen, E.G.

AU - Licht, Tine Rask

AU - Poulsen, Steen Seier

AU - Metzdorff, Stine Broeng

AU - Hansen, Axel Kornerup

AU - Hansen, Camilla Hartmann Friis

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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.

AB - 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.

KW - Faculty of Health and Medical Sciences

KW - γδ T cells

KW - Gut microbiota

KW - Intraepithelial lymphocytes (IELs)

KW - NKG2D

KW - TL1A

U2 - 10.1002/eji.201444528

DO - 10.1002/eji.201444528

M3 - Journal article

C2 - 25404161

SN - 0014-2980

VL - 45

SP - 865

EP - 875

JO - European Journal of Immunology

JF - European Journal of Immunology

IS - 3

ER -