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IL-18Rα-deficient CD4+ T cells induce intestinal inflammation in the CD45RBhi transfer model of colitis despite impaired innate responsiveness

Holmkvist, Petra LU ; Pool, Lieneke LU ; Hägerbrand, Karin LU ; Agace, William W. LU and Rivollier, Aymeric LU (2016) In European Journal of Immunology 46(6). p.1371-1382
Abstract

IL-18 has been implicated in inflammatory bowel disease (IBD), however its role in the regulation of intestinal CD4+ T-cell function remains unclear. Here we show that murine intestinal CD4+ T cells express high levels of IL-18Rα and provide evidence that IL-18Rα expression is induced on these cells subsequent to their entry into the intestinal mucosa. Using the CD45RBhi T-cell transfer colitis model, we show that IL-18Rα is expressed on IFN-γ+, IL-17+, and IL-17+IFN-γ+ effector CD4+ T cells in the inflamed colonic lamina propria (cLP) and mesenteric lymph node (MLN) and is required for the optimal generation and/or maintenance of IFN-γ-producing... (More)

IL-18 has been implicated in inflammatory bowel disease (IBD), however its role in the regulation of intestinal CD4+ T-cell function remains unclear. Here we show that murine intestinal CD4+ T cells express high levels of IL-18Rα and provide evidence that IL-18Rα expression is induced on these cells subsequent to their entry into the intestinal mucosa. Using the CD45RBhi T-cell transfer colitis model, we show that IL-18Rα is expressed on IFN-γ+, IL-17+, and IL-17+IFN-γ+ effector CD4+ T cells in the inflamed colonic lamina propria (cLP) and mesenteric lymph node (MLN) and is required for the optimal generation and/or maintenance of IFN-γ-producing cells in the cLP. In the steady state and during colitis, TCR-independent cytokine-induced IFN-γ and IL-17 production by intestinal CD4+ T cells was largely IL-18Rα−dependent. Despite these findings however, IL-18Rα−deficient CD4+ T cells induced comparable intestinal pathology to WT CD4+ T cells. These findings suggest that IL-18-dependent cytokine induced activation of CD4+ T cells is not critical for the development of T-cell-mediated colitis.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
IFN-γ, IL-18 receptor signaling, Innate responsiveness, T-cell transfer colitis
in
European Journal of Immunology
volume
46
issue
6
pages
12 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:27062602
  • wos:000380752100009
  • scopus:84973652217
ISSN
0014-2980
DOI
10.1002/eji.201545957
language
English
LU publication?
yes
id
f5199f82-cf0d-4dce-86f7-ec305a894399
date added to LUP
2016-07-12 12:36:36
date last changed
2024-01-04 09:51:39
@article{f5199f82-cf0d-4dce-86f7-ec305a894399,
  abstract     = {{<p>IL-18 has been implicated in inflammatory bowel disease (IBD), however its role in the regulation of intestinal CD4<sup>+</sup> T-cell function remains unclear. Here we show that murine intestinal CD4<sup>+</sup> T cells express high levels of IL-18Rα and provide evidence that IL-18Rα expression is induced on these cells subsequent to their entry into the intestinal mucosa. Using the CD45RB<sup>hi</sup> T-cell transfer colitis model, we show that IL-18Rα is expressed on IFN-γ<sup>+</sup>, IL-17<sup>+</sup>, and IL-17<sup>+</sup>IFN-γ<sup>+</sup> effector CD4<sup>+</sup> T cells in the inflamed colonic lamina propria (cLP) and mesenteric lymph node (MLN) and is required for the optimal generation and/or maintenance of IFN-γ-producing cells in the cLP. In the steady state and during colitis, TCR-independent cytokine-induced IFN-γ and IL-17 production by intestinal CD4<sup>+</sup> T cells was largely IL-18Rα−dependent. Despite these findings however, IL-18Rα−deficient CD4<sup>+</sup> T cells induced comparable intestinal pathology to WT CD4<sup>+</sup> T cells. These findings suggest that IL-18-dependent cytokine induced activation of CD4<sup>+</sup> T cells is not critical for the development of T-cell-mediated colitis.</p>}},
  author       = {{Holmkvist, Petra and Pool, Lieneke and Hägerbrand, Karin and Agace, William W. and Rivollier, Aymeric}},
  issn         = {{0014-2980}},
  keywords     = {{IFN-γ; IL-18 receptor signaling; Innate responsiveness; T-cell transfer colitis}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{6}},
  pages        = {{1371--1382}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{European Journal of Immunology}},
  title        = {{IL-18Rα-deficient CD4<sup>+</sup> T cells induce intestinal inflammation in the CD45RB<sup>hi</sup> transfer model of colitis despite impaired innate responsiveness}},
  url          = {{http://dx.doi.org/10.1002/eji.201545957}},
  doi          = {{10.1002/eji.201545957}},
  volume       = {{46}},
  year         = {{2016}},
}