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TL1A Aggravates Cytokine-Induced Acute Gut Inflammation and Potentiates Infiltration of Intraepithelial Natural Killer Cells in Mice

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Standard

TL1A Aggravates Cytokine-Induced Acute Gut Inflammation and Potentiates Infiltration of Intraepithelial Natural Killer Cells in Mice. / Tougaard, Peter; Martinsen, Louise Otterstrøm; Zachariassen, Line Fisker; Krych, Lukasz; Nielsen, Dennis Sandris; Buus, Terkild Brink; Pedersen, Anders Elm; Hansen, Axel Kornerup; Skov, Søren; Hansen, Camilla Hartmann Friis.

I: Inflammatory Bowel Diseases, Bind 25, Nr. 3, 2019, s. 510-523.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Tougaard, P, Martinsen, LO, Zachariassen, LF, Krych, L, Nielsen, DS, Buus, TB, Pedersen, AE, Hansen, AK, Skov, S & Hansen, CHF 2019, 'TL1A Aggravates Cytokine-Induced Acute Gut Inflammation and Potentiates Infiltration of Intraepithelial Natural Killer Cells in Mice', Inflammatory Bowel Diseases, bind 25, nr. 3, s. 510-523. https://doi.org/10.1093/ibd/izy351

APA

Tougaard, P., Martinsen, L. O., Zachariassen, L. F., Krych, L., Nielsen, D. S., Buus, T. B., Pedersen, A. E., Hansen, A. K., Skov, S., & Hansen, C. H. F. (2019). TL1A Aggravates Cytokine-Induced Acute Gut Inflammation and Potentiates Infiltration of Intraepithelial Natural Killer Cells in Mice. Inflammatory Bowel Diseases, 25(3), 510-523. https://doi.org/10.1093/ibd/izy351

Vancouver

Tougaard P, Martinsen LO, Zachariassen LF, Krych L, Nielsen DS, Buus TB o.a. TL1A Aggravates Cytokine-Induced Acute Gut Inflammation and Potentiates Infiltration of Intraepithelial Natural Killer Cells in Mice. Inflammatory Bowel Diseases. 2019;25(3):510-523. https://doi.org/10.1093/ibd/izy351

Author

Tougaard, Peter ; Martinsen, Louise Otterstrøm ; Zachariassen, Line Fisker ; Krych, Lukasz ; Nielsen, Dennis Sandris ; Buus, Terkild Brink ; Pedersen, Anders Elm ; Hansen, Axel Kornerup ; Skov, Søren ; Hansen, Camilla Hartmann Friis. / TL1A Aggravates Cytokine-Induced Acute Gut Inflammation and Potentiates Infiltration of Intraepithelial Natural Killer Cells in Mice. I: Inflammatory Bowel Diseases. 2019 ; Bind 25, Nr. 3. s. 510-523.

Bibtex

@article{e0c811a142724e97b51677b8d42b7dff,
title = "TL1A Aggravates Cytokine-Induced Acute Gut Inflammation and Potentiates Infiltration of Intraepithelial Natural Killer Cells in Mice",
abstract = "BackgroundThe tumor necrosis factor alpha (TNFα)–homologous cytokine TL1A is emerging as a major player in intestinal inflammation. From in vitro experiments on human lymphocytes, TNF-like molecule 1A (TL1A) is known to activate a highly inflammatory lymphoid response in synergy with interleukin (IL)-12 and IL-18. Carriers of specific genetic polymorphisms associated with IL-12, IL-18, or TL1A signaling have increased Crohn{\textquoteright}s disease risk, and all 3 cytokines are upregulated during active disease. The study aim was to investigate whether the type 1–polarizing cytokines IL-12 and IL-18 could directly initiate intestinal pathology in mice and how TL1A would influence the resulting inflammatory response.MethodsConventional barrier-bred and germ-free mice were randomly allocated to different groups and injected twice with different combinations of IL-12, IL-18, and TL1A, and killed 3 days after the first injection. All treatment groups were co-housed and fed a piroxicam-supplemented chow diet.ResultsIntestinal pathology was evident in IL-12- and IL-18-treated mice and highly exacerbated by TL1A in both the colon and ileum. The cytokine-induced intestinal inflammation was characterized by epithelial damage, increased colonic levels of TNFα, IL-1β, IFN-γ, and IL-6, and various chemokines along with gut microbiota alterations exhibiting high abundance of Enterobacteriaceae. Furthermore, the inflamed ileum and colon exhibited a TL1A-specific increased infiltration of intraepithelial natural killer cells co-expressing NKG2D and IL-18Ra and a higher frequency of unconventional T cells in the colonic epithelium. Upon cytokine injection, germ-free mice exhibited similar intraepithelial lymphoid infiltration and increased colonic levels of IFNγ and TNFα.ConclusionsThis study demonstrates that TL1A aggravates IL-12- and IL-18-induced intestinal inflammation in the presence and absence of microbiota.",
keywords = "intraepithelial lymphocytes, NKG2D, cytokine synergy",
author = "Peter Tougaard and Martinsen, {Louise Otterstr{\o}m} and Zachariassen, {Line Fisker} and Lukasz Krych and Nielsen, {Dennis Sandris} and Buus, {Terkild Brink} and Pedersen, {Anders Elm} and Hansen, {Axel Kornerup} and S{\o}ren Skov and Hansen, {Camilla Hartmann Friis}",
year = "2019",
doi = "10.1093/ibd/izy351",
language = "English",
volume = "25",
pages = "510--523",
journal = "Inflammatory Bowel Diseases",
issn = "1078-0998",
publisher = "Lippincott Williams & Wilkins",
number = "3",

}

RIS

TY - JOUR

T1 - TL1A Aggravates Cytokine-Induced Acute Gut Inflammation and Potentiates Infiltration of Intraepithelial Natural Killer Cells in Mice

AU - Tougaard, Peter

AU - Martinsen, Louise Otterstrøm

AU - Zachariassen, Line Fisker

AU - Krych, Lukasz

AU - Nielsen, Dennis Sandris

AU - Buus, Terkild Brink

AU - Pedersen, Anders Elm

AU - Hansen, Axel Kornerup

AU - Skov, Søren

AU - Hansen, Camilla Hartmann Friis

PY - 2019

Y1 - 2019

N2 - BackgroundThe tumor necrosis factor alpha (TNFα)–homologous cytokine TL1A is emerging as a major player in intestinal inflammation. From in vitro experiments on human lymphocytes, TNF-like molecule 1A (TL1A) is known to activate a highly inflammatory lymphoid response in synergy with interleukin (IL)-12 and IL-18. Carriers of specific genetic polymorphisms associated with IL-12, IL-18, or TL1A signaling have increased Crohn’s disease risk, and all 3 cytokines are upregulated during active disease. The study aim was to investigate whether the type 1–polarizing cytokines IL-12 and IL-18 could directly initiate intestinal pathology in mice and how TL1A would influence the resulting inflammatory response.MethodsConventional barrier-bred and germ-free mice were randomly allocated to different groups and injected twice with different combinations of IL-12, IL-18, and TL1A, and killed 3 days after the first injection. All treatment groups were co-housed and fed a piroxicam-supplemented chow diet.ResultsIntestinal pathology was evident in IL-12- and IL-18-treated mice and highly exacerbated by TL1A in both the colon and ileum. The cytokine-induced intestinal inflammation was characterized by epithelial damage, increased colonic levels of TNFα, IL-1β, IFN-γ, and IL-6, and various chemokines along with gut microbiota alterations exhibiting high abundance of Enterobacteriaceae. Furthermore, the inflamed ileum and colon exhibited a TL1A-specific increased infiltration of intraepithelial natural killer cells co-expressing NKG2D and IL-18Ra and a higher frequency of unconventional T cells in the colonic epithelium. Upon cytokine injection, germ-free mice exhibited similar intraepithelial lymphoid infiltration and increased colonic levels of IFNγ and TNFα.ConclusionsThis study demonstrates that TL1A aggravates IL-12- and IL-18-induced intestinal inflammation in the presence and absence of microbiota.

AB - BackgroundThe tumor necrosis factor alpha (TNFα)–homologous cytokine TL1A is emerging as a major player in intestinal inflammation. From in vitro experiments on human lymphocytes, TNF-like molecule 1A (TL1A) is known to activate a highly inflammatory lymphoid response in synergy with interleukin (IL)-12 and IL-18. Carriers of specific genetic polymorphisms associated with IL-12, IL-18, or TL1A signaling have increased Crohn’s disease risk, and all 3 cytokines are upregulated during active disease. The study aim was to investigate whether the type 1–polarizing cytokines IL-12 and IL-18 could directly initiate intestinal pathology in mice and how TL1A would influence the resulting inflammatory response.MethodsConventional barrier-bred and germ-free mice were randomly allocated to different groups and injected twice with different combinations of IL-12, IL-18, and TL1A, and killed 3 days after the first injection. All treatment groups were co-housed and fed a piroxicam-supplemented chow diet.ResultsIntestinal pathology was evident in IL-12- and IL-18-treated mice and highly exacerbated by TL1A in both the colon and ileum. The cytokine-induced intestinal inflammation was characterized by epithelial damage, increased colonic levels of TNFα, IL-1β, IFN-γ, and IL-6, and various chemokines along with gut microbiota alterations exhibiting high abundance of Enterobacteriaceae. Furthermore, the inflamed ileum and colon exhibited a TL1A-specific increased infiltration of intraepithelial natural killer cells co-expressing NKG2D and IL-18Ra and a higher frequency of unconventional T cells in the colonic epithelium. Upon cytokine injection, germ-free mice exhibited similar intraepithelial lymphoid infiltration and increased colonic levels of IFNγ and TNFα.ConclusionsThis study demonstrates that TL1A aggravates IL-12- and IL-18-induced intestinal inflammation in the presence and absence of microbiota.

KW - intraepithelial lymphocytes

KW - NKG2D

KW - cytokine synergy

U2 - 10.1093/ibd/izy351

DO - 10.1093/ibd/izy351

M3 - Journal article

C2 - 30462201

VL - 25

SP - 510

EP - 523

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

SN - 1078-0998

IS - 3

ER -

ID: 215358470