| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Berlin, Germany;
Medical Clinic 1 (Gastroenterology, Rheumatology, Infectiology), University Hospital Charité, Berlin, Germany;
CRBA Inflammation, Schering AG, Berlin, Germany;
Department of Dermatology, University Hospital Charité, Berlin, Germany; and
¶ Institute of Medical Immunology, University Hospital Charité, Berlin, Germany
Crohn's disease (CD) is a common, chronic, inflammatory bowel disease characterized by intestinal infiltration of activated immune cells and distortion of the intestinal architecture. In this study, we demonstrate that IL-22, a cytokine that is mainly produced by activated Th1 and Th17 cells, was present in high quantities in the blood of CD patients in contrast to IFN-
and IL-17. In a mouse colitis model, IL-22 mRNA expression was elevated predominantly in the inflamed intestine but also in the mesenteric lymph nodes. IL-22BP, the soluble receptor for IL-22, demonstrated an affinity to IL-22 that was at least 4-fold higher than its membrane-bound receptor, and its strong constitutive expression in the intestine and lymph nodes was decreased in the inflamed intestine. To investigate the possible role of systemic IL-22 in CD, we then administered IL-22 to healthy mice and found an up-regulation of LPS-binding protein (LBP) blood levels reaching concentrations known to neutralize LPS. This systemic up-regulation was associated with increased hepatic but not renal or pulmonary LBP mRNA levels. IL-22 also enhanced the secretion of LBP in human primary hepatocytes and HepG2 hepatoma cells in vitro. This increase was mainly transcriptionally regulated and synergistic with that of other LBP inducers. Finally, elevated LBP levels were detected in CD patients and the mouse colitis model. These data suggest that systemic IL-22 may contribute to the prevention of systemic inflammation provoked by LPS present in the blood of CD patients through its induction of hepatic LBP.
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 K.W. and E.W. contributed equally to this work.
2 Address correspondence and reprint requests to Dr. Robert Sabat, Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, Campus Charité Mitte, University Hospital Charité, Charitéplatz 1, Berlin, Germany. E-mail address: robert.sabat{at}charite.de
3 Abbreviations used in this paper: IL-22BP, IL-22-binding protein; CD, Crohn’s disease; LBP, LPS-binding protein; DSS, dextran sulfate sodium; HPRT, hypoxanthine phosphoribosyltransferase 1; RU, resonance units; CDAI, Crohn’s disease activity index; SAPK, stress-activated protein kinase.
This article has been cited by other articles:
|
|
 |
|
  B. Gao, S. Radaeva, and O. Park Liver natural killer and natural killer T cells: immunobiology and emerging roles in liver diseases J. Leukoc. Biol., September 1, 2009; 86(3): 513 - 528. [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]
|
|
|
|
 |
|
 S. Siegemund, N. Schutze, S. Schulz, K. Wolk, K. Nasilowska, R. K. Straubinger, R. Sabat, and G. Alber Differential IL-23 requirement for IL-22 and IL-17A production during innate immunity against Salmonella enterica serovar Enteritidis Int. Immunol., May 1, 2009; 21(5): 555 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Cheng, Z Guo, H Xu, D Yan, and Q Li Decreased plasma IL22 levels, but not increased IL17 and IL23 levels, correlate with disease activity in patients with systemic lupus erythematosus Ann Rheum Dis, April 1, 2009; 68(4): 604 - 606. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Wahl, W. Muller, F. Leithauser, G. Adler, F. Oswald, J. Reimann, R. Schirmbeck, A. Seier, J. M. Weiss, B. Prochnow, et al. IL-20 Receptor 2 Signaling Down-Regulates Antigen-Specific T Cell Responses J. Immunol., January 15, 2009; 182(2): 802 - 810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Schulz, G. Kohler, N. Schutze, J. Knauer, R. K. Straubinger, A. A. Chackerian, E. Witte, K. Wolk, R. Sabat, Y. Iwakura, et al. Protective Immunity to Systemic Infection with Attenuated Salmonella enterica serovar Enteritidis in the Absence of IL-12 Is Associated with IL-23-Dependent IL-22, but Not IL-17 J. Immunol., December 1, 2008; 181(11): 7891 - 7901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D H Adams, B Eksteen, and S M Curbishley Immunology of the gut and liver: a love/hate relationship Gut, June 1, 2008; 57(6): 838 - 848. [Full Text] [PDF]
|
|
|
|
|
|
K. Wolk, K. Witte, E. Witte, S. Proesch, G. Schulze-Tanzil, K. Nasilowska, J. Thilo, K. Asadullah, W. Sterry, H.-D. Volk, et al. Maturing dendritic cells are an important source of IL-29 and IL-20 that may cooperatively increase the innate immunity of keratinocytes J. Leukoc. Biol., May 1, 2008; 83(5): 1181 - 1193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Flanagan, Z. Modrusan, J. Cornelius, A. Chavali, I. Kasman, L. Komuves, L. Mo, and L. Diehl Intestinal Epithelial Cell Up-Regulation of LY6 Molecules during Colitis Results in Enhanced Chemokine Secretion J. Immunol., March 15, 2008; 180(6): 3874 - 3881. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
