IL-1β mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4 + Th17 cells

Margherita Coccia, Oliver J. Harrison, Chris Schiering, Mark Asquith, Burkhard Becher, Fiona Powrie, Kevin J. Maloy

Research output: Contribution to journalArticle

260 Citations (Scopus)

Abstract

Although very high levels of interleukin (IL)-1β are present in the intestines of patients suffering from inflammatory bowel diseases (IBD), little is known about the contribution of IL-1β to intestinal pathology. Here, we used two complementary models of chronic intesti- nal inflammation to address the role of IL-1β in driving innate and adaptive pathology in the intestine. We show that IL-1β promotes innate immune pathology in Helicobacter hepaticus-triggered intestinal inflammation by augmenting the recruitment of granulocytes and the accumulation and activation of innate lymphoid cells (ILCs). Using a T cell transfer colitis model, we demonstrate a key role for T cell-specific IL-1 receptor (IL-1R) signals in the accumulation and survival of pathogenic CD4 + T cells in the colon. Furthermore, we show that IL-1β promotes Th17 responses from CD4 + T cells and ILCs in the intestine, and we describe synergistic interactions between IL-1β and IL-23 signals that sustain innate and adaptive inflammatory responses in the gut. These data identify multiple mechanisms through which IL-1β promotes intestinal pathology and suggest that targeting IL-1β may represent a useful therapeutic approach in IBD.

Original languageEnglish (US)
Pages (from-to)1595-1609
Number of pages15
JournalJournal of Experimental Medicine
Volume209
Issue number9
DOIs
StatePublished - Aug 2012
Externally publishedYes

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Th17 Cells
Interleukin-17
Interleukin-1
Lymphocytes
Inflammation
Pathology
Intestines
T-Lymphocytes
Inflammatory Bowel Diseases
Helicobacter hepaticus
Interleukin-23
Interleukin-1 Receptors
Colitis
Granulocytes
Colon
Survival

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

IL-1β mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4 + Th17 cells. / Coccia, Margherita; Harrison, Oliver J.; Schiering, Chris; Asquith, Mark; Becher, Burkhard; Powrie, Fiona; Maloy, Kevin J.

In: Journal of Experimental Medicine, Vol. 209, No. 9, 08.2012, p. 1595-1609.

Research output: Contribution to journalArticle

Coccia, Margherita ; Harrison, Oliver J. ; Schiering, Chris ; Asquith, Mark ; Becher, Burkhard ; Powrie, Fiona ; Maloy, Kevin J. / IL-1β mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4 + Th17 cells. In: Journal of Experimental Medicine. 2012 ; Vol. 209, No. 9. pp. 1595-1609.
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