| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Institut National de la Santé et de la Recherche Médicale, Unité 844, Montpellier, France;
Institut National de la Santé et de la Recherche Médicale, Unité mixte 564, Université d’Angers, Angers, France; and
Institut Universitaire de Recherche Clinique, Montpellier, France
Chronic inflammatory diseases are characterized by local tissue injury caused by immunocompetent cells, in particular CD4+ T lymphocytes, that are involved in the pathogenesis of these disorders via the production of distinctive sets of cytokines. Here, we have characterized single CD4+ T cells that infiltrate inflamed tissue taken from patients with psoriasis, Crohn’s disease, rheumatoid arthritis, or allergic asthma. Results from a cytokine production and gene profile analysis identified a population of in vivo differentiatedretinoid-related orphan receptor 
-expressing T cells, producing high levels of IL-17, that can represent up to 30% of infiltrating T lymphocytes. Activated Th17 cells produced IL-26, TNF-
, lymphotoxin-β, and IL-22. IL-17 and IL-22 concentrations secreted by tissue infiltrating Th17 cells could reach up to 100 nM and were inversely correlated with the production of Th1- and Th2-associated cytokines. In addition, tissue-infiltrating Th17 cells are also characterized by high cell surface expression of CCR6, a chemokine receptor that was not expressed by Th1 and Th2 cells, isolated from the same lesions, and by the production of CCL20/MIP3, a CCR6 ligand, associated with tissue infiltration. Culture supernatants of activated Th17 cells, isolated from psoriatic lesions, induced the expression of gene products associated with inflammation and abnormal keratinocyte differentiation in an IL-17 and IL-22-dependent manner. These results show that tissue-infiltrating Th17 cells contribute to human chronic inflammatory disease via the production of several inflammatory cytokines and the creation of an environment contributing to their migration and sequestration at sites of inflammation.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Address correspondence and reprint requests to Dr. Hugues Gascan, Institut National de la Santé et de la Recherche Médicale, Unité mixte 564, Université d’Angers, 49033 Angers Cedex, France. E-mail address: gascan{at}univ-angers.fr or Dr. Hans Yssel, Institut National de la Santé et de la Recherche Médicale, Unité 844, 80 Rue Augustin Fliche, Montpellier Cedex 34091, France. E-mail address: hans.yssel{at}inserm.fr
2 Abbreviations used in this paper: RORC, retinoid-related orphan receptor ; LT, lymphotoxin; RORt, retinoid-related orphan receptor t.
This article has been cited by other articles:
|
|
 |
|
  L Rovedatti, T Kudo, P Biancheri, M Sarra, C H Knowles, D S Rampton, G R Corazza, G Monteleone, A Di Sabatino, and T T MacDonald Differential regulation of interleukin 17 and interferon {gamma} production in inflammatory bowel disease Gut, December 1, 2009; 58(12): 1629 - 1636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Shi, M. Ramaswamy, B. P. Vistica, C. A. Cox, C. Tan, E. F. Wawrousek, R. M. Siegel, and I. Gery Unlike Th1, Th17 Cells Mediate Sustained Autoimmune Inflammation and Are Highly Resistant to Restimulation-Induced Cell Death J. Immunol., December 1, 2009; 183(11): 7547 - 7556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Miossec, T. Korn, and V. K. Kuchroo Interleukin-17 and Type 17 Helper T Cells N. Engl. J. Med., August 27, 2009; 361(9): 888 - 898. [Full Text] [PDF]
|
|
|
|
|
|
G. Murugaiyan, A. Mittal, R. Lopez-Diego, L. M. Maier, D. E. Anderson, and H. L. Weiner IL-27 Is a Key Regulator of IL-10 and IL-17 Production by Human CD4+ T Cells J. Immunol., August 15, 2009; 183(4): 2435 - 2443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Brand Crohn's disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease Gut, August 1, 2009; 58(8): 1152 - 1167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Migita, T. Koga, T. Torigoshi, Y. Maeda, T. Miyashita, Y. Izumi, Y. Aiba, A. Komori, M. Nakamura, S. Motokawa, et al. Serum amyloid A protein stimulates CCL20 production in rheumatoid synoviocytes Rheumatology, July 1, 2009; 48(7): 741 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nistala and L. R. Wedderburn Th17 and regulatory T cells: rebalancing pro- and anti-inflammatory forces in autoimmune arthritis Rheumatology, June 1, 2009; 48(6): 602 - 606. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Beriou, C. M. Costantino, C. W. Ashley, L. Yang, V. K. Kuchroo, C. Baecher-Allan, and D. A. Hafler IL-17-producing human peripheral regulatory T cells retain suppressive function Blood, April 30, 2009; 113(18): 4240 - 4249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Phan and M. L. Disis Tumor-Specific Th1 Lymphocytes: Modulation of the Tumor Microenvironment to Enhance Cross-Priming Am. Assoc. Cancer Res. Educ. Book, April 18, 2009; 2009(1): 199 - 202. [Full Text] [PDF]
|
|
|
|
 |
|
 H. G. Evans, N. J. Gullick, S. Kelly, C. Pitzalis, G. M. Lord, B. W. Kirkham, and L. S. Taams In vivo activated monocytes from the site of inflammation in humans specifically promote Th17 responses PNAS, April 14, 2009; 106(15): 6232 - 6237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Kleinschek, K. Boniface, S. Sadekova, J. Grein, E. E. Murphy, S. P. Turner, L. Raskin, B. Desai, W. A. Faubion, R. de Waal Malefyt, et al. Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation J. Exp. Med., March 16, 2009; 206(3): 525 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Hou, H. S. Kang, and B. S. Kim Th17 cells enhance viral persistence and inhibit T cell cytotoxicity in a model of chronic virus infection J. Exp. Med., February 16, 2009; 206(2): 313 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Tangye, M. C. Cook, and D. A. Fulcher Insights into the Role of STAT3 in Human Lymphocyte Differentiation as Revealed by the Hyper-IgE Syndrome J. Immunol., January 1, 2009; 182(1): 21 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Wakkach, A. Mansour, R. Dacquin, E. Coste, P. Jurdic, G. F. Carle, and C. Blin-Wakkach Bone marrow microenvironment controls the in vivo differentiation of murine dendritic cells into osteoclasts Blood, December 15, 2008; 112(13): 5074 - 5083. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Annunziato, L. Cosmi, F. Liotta, E. Maggi, and S. Romagnani The phenotype of human Th17 cells and their precursors, the cytokines that mediate their differentiation and the role of Th17 cells in inflammation Int. Immunol., November 1, 2008; 20(11): 1361 - 1368. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
