| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B Kinase Complex 
Kinase Activity Controls Chemokine and High Endothelial Venule Gene Expression in Lymph Nodes and Nasal-Associated Lymphoid Tissue1
* Department of Epidemiology and Public Health, Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520; and
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093
The lymphotoxin (LT) 
receptor plays a critical role in secondary lymphoid organogenesis and the classical and alternative NF-
B pathways have been implicated in this process. IKK
is a key molecule for the activation of the alternative NF-B pathway. However, its precise role and target genes in secondary lymphoid organogenesis remain unknown, particularly with regard to high endothelial venules (HEV). In this study, we show that IKKAA mutant mice, who lack inducible kinase activity, have hypocellular lymph nodes (LN) and nasal-associated lymphoid (NALT) tissue characterized by marked defects in microarchitecture and HEV. In addition, IKKAA LNs showed reduced lymphoid chemokine CCL19, CCL21, and CXCL13 expression. IKKAA LN- and NALT-HEV were abnormal in appearance with reduced expression of peripheral node addressin (PNAd) explained by a severe reduction in the HEV-associated proteins, glycosylation-dependent cell adhesion molecule 1 (GlyCAM-1), and high endothelial cell sulfotransferase, a PNAd-generating enzyme that is a target of LT. In this study, analysis of LT–/– mice identifies GlyCAM-1 as another LT-dependent gene. In contrast, TNFRI–/– mice, which lose classical NF-B pathway activity but retain alternative NF-B pathway activity, showed relatively normal GlyCAM-1 and HEC-6ST expression in LN-HEV. In addition, in this communication, it is demonstrated that LTR is prominently expressed on LN- and NALT-HEV. Thus, these data reveal a critical role for IKK in LN and NALT development, identify GlyCAM-1 and high endothelial cell sulfotransferase as new IKK-dependent target genes, and suggest that LTR signaling on HEV can regulate HEV-specific gene expression.
This article has been cited by other articles:
|
|
 |
|
  J. Wang, R. R. Seethala, Q. Zhang, W. Gooding, C. van Waes, H. Hasegawa, and R. L. Ferris Autocrine and Paracrine Chemokine Receptor 7 Activation in Head and Neck Cancer: Implications for Therapy J Natl Cancer Inst, April 2, 2008; 100(7): 502 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Madge, M. S. Kluger, J. S. Orange, and M. J. May Lymphotoxin-{alpha}1{beta}2 and LIGHT Induce Classical and Noncanonical NF-{kappa}B-Dependent Proinflammatory Gene Expression in Vascular Endothelial Cells J. Immunol., March 1, 2008; 180(5): 3467 - 3477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. De Trez, K. Schneider, K. Potter, N. Droin, J. Fulton, P. S. Norris, S.-w. Ha, Y.-X. Fu, T. Murphy, K. M. Murphy, et al. The Inhibitory HVEM-BTLA Pathway Counter Regulates Lymphotoxin Receptor Signaling to Achieve Homeostasis of Dendritic Cells J. Immunol., January 1, 2008; 180(1): 238 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Guo, D. Weih, E. Meier, and F. Weih Constitutive alternative NF-{kappa}B signaling promotes marginal zone B-cell development but disrupts the marginal sinus and induces HEV-like structures in the spleen Blood, October 1, 2007; 110(7): 2381 - 2389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. White, D. Carragher, S. Parnell, A. Msaki, N. Perkins, P. Lane, E. Jenkinson, G. Anderson, and J. H. Caamano Lymphotoxin a-dependent and -independent signals regulate stromal organizer cell homeostasis during lymph node organogenesis Blood, September 15, 2007; 110(6): 1950 - 1959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. Furtado, T. Marinkovic, A. P. Martin, A. Garin, B. Hoch, W. Hubner, B. K. Chen, E. Genden, M. Skobe, and S. A. Lira Lymphotoxin beta receptor signaling is required for inflammatory lymphangiogenesis in the thyroid PNAS, March 20, 2007; 104(12): 5026 - 5031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Liao, K. Bentley, M. Lebrun, W. Lesslauer, F. H. Ruddle, and N. H. Ruddle Transgenic LacZ under control of Hec-6st regulatory sequences recapitulates endogenous gene expression on high endothelial venules PNAS, March 13, 2007; 104(11): 4577 - 4582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pacher, J. S. Beckman, and L. Liaudet Nitric Oxide and Peroxynitrite in Health and Disease Physiol Rev, January 1, 2007; 87(1): 315 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fukuyama, T. Nagatake, D.-Y. Kim, K. Takamura, E. J. Park, T. Kaisho, N. Tanaka, Y. Kurono, and H. Kiyono Cutting Edge: Uniqueness of Lymphoid Chemokine Requirement for the Initiation and Maturation of Nasopharynx-Associated Lymphoid Tissue Organogenesis J. Immunol., October 1, 2006; 177(7): 4276 - 4280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Liao and N. H. Ruddle Synchrony of high endothelial venules and lymphatic vessels revealed by immunization. J. Immunol., September 1, 2006; 177(5): 3369 - 3379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Levrand, B. Pesse, F. Feihl, B. Waeber, P. Pacher, J. Rolli, M.-D. Schaller, and L. Liaudet Peroxynitrite Is a Potent Inhibitor of NF-{kappa}B Activation Triggered by Inflammatory Stimuli in Cardiac and Endothelial Cell Lines J. Biol. Chem., October 14, 2005; 280(41): 34878 - 34887. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
