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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
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
external identifiers
  • 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
2016-07-15 14:58:37
@misc{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},
  keyword      = {IFN-γ,IL-18 receptor signaling,Innate responsiveness,T-cell transfer colitis},
  language     = {eng},
  month        = {06},
  number       = {6},
  pages        = {1371--1382},
  publisher    = {ARRAY(0x88ebb68)},
  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},
  volume       = {46},
  year         = {2016},
}