Article

O’Connor W, Kamanaka M, Booth CJ et al.A protective function for interleukin 17A in T cell-mediated intestinal inflammation. Nat Immunol 10:603-609

Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
Nature Immunology (Impact Factor: 24.97). 07/2009; 10(6):603-9. DOI: 10.1038/ni.1736
Source: PubMed

ABSTRACT 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.

Download full-text

Full-text

Available from: Richard A Flavell, Aug 24, 2015
0 Followers
 · 
141 Views
  • Source
    • "Instead, RORct-dependent expression of GM-CSF from Th cells activated by IL-23 has a pivotal role in the pathogenesis; Th cell-derived GM-CSF augments the infiltration of CD45 hi CD11b + myeloid cells into CNS and contributes to the development of EAE (Codarri et al. 2011). In murine colitis models, IL-17A production from CD4 + T cells is protective because IL-17A directly suppresses the development of colitogenic Th1 cells via IL-17R expressed on activated CD4 + T cells (O'Connor et al. 2009). In contrast, as in other autoimmune disease models, IL-23 accelerates the severity of murine colitis (Ahern et al. 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: IL-17-producing T helper (Th17) cells comprise a distinct Th subset involved in epithelial cell- and neutrophil-mediated immune responses against extracellular microbes. At the same time, Th17 cells play significant roles in the development of autoimmune diseases including rheumatoid arthritis and multiple sclerosis. Since the identification of Th17 cells approximately a decade ago, the molecular mechanisms of their differentiation have been intensively studied and a number of signaling cascades and transcription factors have been shown to be involved. Here, we review the current knowledge regarding the function of Th17 cells in vivo as well as several key concepts for the molecular mechanisms of Th17 differentiation. We also discuss the emerging roles of phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin complex 1 (mTORC1) and hypoxia-inducible factor 1 (HIF-1) in the differentiation of Th17 cells.
    Genes to Cells 02/2013; 18(4). DOI:10.1111/gtc.12039 · 2.86 Impact Factor
  • Source
    • "Th17 cells produce IL-17 and are involved in the development of a wide range of autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, psoriasis, and inflammatory bowel disease [43]. Both protective and pathogenic effects have been described for IL-17 in distinct autoimmune diseases [44] [45]. The precise role of IL-17 in atherosclerosis is still controversial because of contradictory publications on the subject [46]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Atherosclerosis has been clearly demonstrated to be a chronic inflammatory disease of the arterial wall. Both cells of the innate and the acquired immune system, particularly monocytes and T lymphocytes, are implicated in the atherogenic process, producing different cytokines with pro- and anti-inflammatory effects. The majority of pathogenic T cells involved in atherosclerosis are of the Th1 profile, that has been correlated positively with coronary artery disease. Many studies conducted to evaluate the molecular factors responsible for the activation of T cells have demonstrated that the main antigenic targets in atherosclerosis are modified endogenous structures. These self-molecules activate autoimmune reactions mainly characterized by the production of Th1 cytokines, thus sustaining the inflammatory mechanisms involved in endothelial dysfunction and plaque development. In this paper we will summarize the different T-cell subsets involved in atherosclerosis and the best characterized autoantigens involved in cardiovascular inflammation.
    The Scientific World Journal 12/2012; 2012:157534. DOI:10.1100/2012/157534 · 1.73 Impact Factor
  • Source
    • "Quantitative real-time PCR was performed as previously described (Horsley et al., 2008; O'Connor et al., 2009). The following accession numbers were used for the Taqman primers: Mm00444241_m1 (IL- 22) and Mm00663697_m1 (IL-22Ra). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Skin wound repair requires complex and highly coordinated interactions between keratinocytes, fibroblasts, and immune cells to restore the epidermal barrier and tissue architecture after acute injury. The cytokine IL-22 mediates unidirectional signaling from immune cells to epithelial cells during injury of peripheral tissues such as the liver and colon, where IL-22 causes epithelial cells to produce antibacterial proteins, express mucins, and enhance epithelial regeneration. In this study, we used IL-22(-/-) mice to investigate the in vivo role for IL-22 in acute skin wounding. We found that IL-22(-/-) mice displayed major defects in the skin's dermal compartment after full-thickness wounding. We also found that IL-22 signaling is active in fibroblasts, using in vitro assays with primary fibroblasts, and that IL-22 directs extracellular matrix (ECM) gene expression and myofibroblast differentiation both in vitro and in vivo. These data define roles of IL-22 beyond epithelial cross talk, and suggest that IL-22 has a previously unidentified role in skin repair by mediating interactions between immune cells and fibroblasts.Journal of Investigative Dermatology advance online publication, 6 December 2012; doi:10.1038/jid.2012.463.
    Journal of Investigative Dermatology 12/2012; 133(5). DOI:10.1038/jid.2012.463 · 6.37 Impact Factor
Show more