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Transcription factor c-Rel plays a crucial role in driving anti-CD40-mediated innate colitis.

Visekruna, A; Linnerz, T; Martinic, V; Vachharajani, N; Hartmann, S; Harb, H; Joeris, Thorsten LU ; Pfefferle, P I; Hofer, M J and Steinhoff, U (2015) In Mucosal Immunology 8(2). p.307-315
Abstract
Genetic and environmental factors, including the commensal microbiota, have a crucial role in the development of inflammatory bowel disease. Aberrant activation of the transcription factor NF-κB is associated with chronic intestinal inflammation in mice and humans. Recently, an emerging family of innate lymphoid cells (ILCs) has been identified at mucosal sites contributing to the maintenance of gut homeostasis and intestinal immunopathology. Here, we show that the NF-κB protein c-Rel regulates the inflammatory potential of colonic IFN-γ(+)Thy1(+) ILCs to induce anti-CD40-mediated colitis in rag1(-/-) mice. Stimulation of dendritic cells (DCs) with anti-CD40 or CD40L led to translocation of c-Rel into the nucleus resulting in induction of... (More)
Genetic and environmental factors, including the commensal microbiota, have a crucial role in the development of inflammatory bowel disease. Aberrant activation of the transcription factor NF-κB is associated with chronic intestinal inflammation in mice and humans. Recently, an emerging family of innate lymphoid cells (ILCs) has been identified at mucosal sites contributing to the maintenance of gut homeostasis and intestinal immunopathology. Here, we show that the NF-κB protein c-Rel regulates the inflammatory potential of colonic IFN-γ(+)Thy1(+) ILCs to induce anti-CD40-mediated colitis in rag1(-/-) mice. Stimulation of dendritic cells (DCs) with anti-CD40 or CD40L led to translocation of c-Rel into the nucleus resulting in induction of expression of interleukin-12 (IL-12) and IL-23, key regulators of innate cell-induced colitis. While c-Rel deficiency completely abrogated anti-CD40-induced colitis, adoptively transferred wild-type DCs were able to induce pronounced colonic inflammation in rag1(-/-)rel(-/-) mice. In summary, these results suggest that the expression of c-Rel in DCs is essential for initiating anti-CD40-mediated intestinal pathogenesis.Mucosal Immunology advance online publication, 6 August 2014; doi:10.1038/mi.2014.68. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Mucosal Immunology
volume
8
issue
2
pages
307 - 315
publisher
Nature Publishing Group
external identifiers
  • pmid:25100292
  • wos:000349681200008
  • scopus:84922700554
ISSN
1933-0219
DOI
10.1038/mi.2014.68
language
English
LU publication?
yes
id
6cc7f59e-dd3a-4275-bfba-98b30348f476 (old id 4615453)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25100292?dopt=Abstract
date added to LUP
2014-09-04 18:11:33
date last changed
2017-09-10 03:15:01
@article{6cc7f59e-dd3a-4275-bfba-98b30348f476,
  abstract     = {Genetic and environmental factors, including the commensal microbiota, have a crucial role in the development of inflammatory bowel disease. Aberrant activation of the transcription factor NF-κB is associated with chronic intestinal inflammation in mice and humans. Recently, an emerging family of innate lymphoid cells (ILCs) has been identified at mucosal sites contributing to the maintenance of gut homeostasis and intestinal immunopathology. Here, we show that the NF-κB protein c-Rel regulates the inflammatory potential of colonic IFN-γ(+)Thy1(+) ILCs to induce anti-CD40-mediated colitis in rag1(-/-) mice. Stimulation of dendritic cells (DCs) with anti-CD40 or CD40L led to translocation of c-Rel into the nucleus resulting in induction of expression of interleukin-12 (IL-12) and IL-23, key regulators of innate cell-induced colitis. While c-Rel deficiency completely abrogated anti-CD40-induced colitis, adoptively transferred wild-type DCs were able to induce pronounced colonic inflammation in rag1(-/-)rel(-/-) mice. In summary, these results suggest that the expression of c-Rel in DCs is essential for initiating anti-CD40-mediated intestinal pathogenesis.Mucosal Immunology advance online publication, 6 August 2014; doi:10.1038/mi.2014.68.},
  author       = {Visekruna, A and Linnerz, T and Martinic, V and Vachharajani, N and Hartmann, S and Harb, H and Joeris, Thorsten and Pfefferle, P I and Hofer, M J and Steinhoff, U},
  issn         = {1933-0219},
  language     = {eng},
  number       = {2},
  pages        = {307--315},
  publisher    = {Nature Publishing Group},
  series       = {Mucosal Immunology},
  title        = {Transcription factor c-Rel plays a crucial role in driving anti-CD40-mediated innate colitis.},
  url          = {http://dx.doi.org/10.1038/mi.2014.68},
  volume       = {8},
  year         = {2015},
}