A protective function for interleukin 17A in T cell–mediated intestinal inflammation

By William O'Connor, M. Kamanaka, C. Booth, T. Town, S. Nakae, Y. Iwakura, J. Kolls, R. Flavell. Nature Immunology, 2009

832 citations recorded by the source corpus.

Interleukin 23 (IL-23) and IL-17 have been linked to the pathogenesis of several chronic inflammatory disorders, including inflammatory bowel disease. Yet as an important function for IL-23 is emerging, the function of IL-17 in inflammatory bowel disease remains unclear. Here we demonstrate IL-17A-mediated protection in the CD45RBhi transfer model of colitis. An accelerated wasting disease elicited by T cells deficient in IL-17A correlated with higher expression of genes encoding T helper type 1–type cytokines in colon tissue. IL-17A also modulated T helper type 1 polarization in vitro. Furthermore, T cells deficient in the IL-17 receptor elicited an accelerated, aggressive wasting disease relative to that elicited by wild-type T cells in recipient mice. Our data demonstrate a protective function for IL-17 and identify T cells as not only the source but also a target of IL-17 in vivo.

Subfields: Genetics, Immunology

View Paper: https://www.semanticscholar.org/paper/f3ed06b59c3c3665da1952afb82405aab9d1505e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. Aviv Regev
2. F. Powrie
3. A. Shalek
4. J. O’Shea
5. P. Pandolfi
6. T. Mak
7. Rahul Satija
8. Alexander Y. Rudensky

In Immunology

1. Aviv Regev
2. Alexander Y. Rudensky
3. J. O’Shea
4. V. Kuchroo
5. Nir Yosef
6. A. Chaudhry
7. R. Flavell
8. F. Powrie

Citations in the corpus

• Th17 cells express interleukin-10 receptor and are controlled by Foxp3− and Foxp3+ regulatory CD4+ T cells in an interleukin-10 dependent manner (2011, methodology): “Each section was evaluated by a semiquantitative criterion-based method (score 0–5) as described before (O’Connor et al., 2009).”
• IL-23-Independent IL-17 Production Regulates Intestinal Epithelial Permeability (2015, neutral): “IL-17A neutralization increases tissue damage in a dextran sodium sulfate (DSS) model of IBD (Ogawa et al., 2004), and IL-17Aor IL-17 receptor alpha (RA)-deficient T cells results in exacerbated colitis when transferred into RAG-1-deficient recipients (O’Connor et al., 2009).”
• Type I interferon: friend or foe? (2010, background): “IFN- is a common and effective treatment for reducing disease recurrence in multiple sclerosis (Noseworthy et al., 2000; Comi, 2009).”
• Diverse Targets of the Transcription Factor STAT3 Contribute to T Cell Pathogenicity and Homeostasis (2010, background): “However, these findings might be explained by reduced IL-17 production, which has recently been reported to inhibit IFN-g production in the setting of colitis (O’Connor et al., 2009).”
• Single-cell Genomics Unveils Critical Regulators of Th17 cell Pathogenicity (2015, background): “Finally, a population-based signature comparing profiles of EAE Th17 cells to lamina propria lymphocyte (LPL) Th17 cells (Supplemental Experimental Procedures and Figure S3), which are known to assume a regulatory phenotype (Esplugues et al., 2011; O’Connor et al., 2009), correlates with PC1 in vivo”