| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Thomas E. Starzl Transplantation Institute and Department of Surgery,
Department of Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; and
Institute of Clinical Immunology and Transfusion Medicine, Justus-Liebig University, Giessen, Germany
Signaling via TLRs results in dendritic cell (DC) activation/maturation and plays a critical role in the outcome of primary immune responses. So far, no data exist concerning TLR expression by liver DC, generally regarded as less immunostimulatory than secondary lymphoid tissue DC. Because the liver lies directly downstream from the gut, it is constantly exposed to bacterial LPS, a TLR4 ligand. We examined TLR4 expression by freshly isolated, flow-sorted C57BL/10 mouse liver DC compared with spleen DC. Real-time PCR revealed that liver CD11c+CD8
– (myeloid) and CD11c+CD8+ ("lymphoid-related") DC expressed lower TLR4 mRNA compared with their splenic counterparts. Lower TLR4 expression correlated with reduced capacity of LPS (10 ng/ml) but not anti-CD40-stimulated liver DC to induce naive allogeneic (C3H/HeJ) T cell proliferation. By contrast to LPS-stimulated splenic DC, these LPS-activated hepatic DC induced alloantigen-specific T cell hyporesponsiveness in vitro, correlated with deficient Th1 (IFN-
) and Th2 (IL-4) responses. When higher LPS concentrations (
100 ng/ml) were tested, the capacity of liver DC to induce proliferation of T cells and Th1-type responses was enhanced, but remained inferior to that of splenic DC. Hepatic DC activated by LPS in vivo were inferior allogeneic T cell stimulators compared with splenic DC, whereas adoptive transfer of LPS-stimulated (10 ng/ml) liver DC induced skewing toward Th2 responses. These data suggest that comparatively low expression of TLR4 by liver DC may limit their response to specific ligands, resulting in reduced or altered activation of hepatic adaptive immune responses.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  A Mencin, J Kluwe, and R F Schwabe Toll-like receptors as targets in chronic liver diseases Gut, May 1, 2009; 58(5): 704 - 720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Jiang, R. Sun, R. Zhou, H. Wei, and Z. Tian TLR-9 Activation Aggravates Concanavalin A-Induced Hepatitis via Promoting Accumulation and Activation of Liver CD4+ NKT Cells J. Immunol., March 15, 2009; 182(6): 3768 - 3774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Natarajan, J. Kim, and D. G. Remick Acute Pulmonary Lipopolysaccharide Tolerance Decreases TNF-{alpha} without Reducing Neutrophil Recruitment J. Immunol., December 15, 2008; 181(12): 8402 - 8408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Zeng, H. Li, Y. Liu, Z. Zhang, Y. Zhang, and R. Yang Tumor-Induced Suppressor of Cytokine Signaling 3 Inhibits Toll-like Receptor 3 Signaling in Dendritic Cells via Binding to Tyrosine Kinase 2 Cancer Res., July 1, 2008; 68(13): 5397 - 5404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. D. Kim, T. H. Terwey, J. L. Zakrzewski, D. Suh, A. A. Kochman, M. E. Chen, C. G. King, C. Borsotti, J. Grubin, O. M. Smith, et al. Organ-derived dendritic cells have differential effects on alloreactive T cells Blood, March 1, 2008; 111(5): 2929 - 2940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Takenaka, E. Safroneeva, Z. Xing, and J. Gauldie Dendritic Cells Derived from Murine Colonic Mucosa Have Unique Functional and Phenotypic Characteristics J. Immunol., June 15, 2007; 178(12): 7984 - 7993. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Lau, M. Abe, and A. W. Thomson Ethanol affects the generation, cosignaling molecule expression, and function of plasmacytoid and myeloid dendritic cell subsets in vitro and in vivo J. Leukoc. Biol., May 1, 2006; 79(5): 941 - 953. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
