|
|
Blood, 15 March 2005, Vol. 105, No. 6, pp. 2449-2457.
Prepublished online as a Blood First Edition Paper on November 9, 2004; DOI 10.1182/blood-2004-06-2289.
 Previous Article | Next Article 
Submitted June 17, 2004
Accepted November 7, 2004
WHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitization to CXCL12
Karl Balabanian, Bernard Lagane, Jose L Pablos, Lysiane Laurent, Thierry Planchenault, Olivier Verola, Celeste Lebbe, Delphine Kerob, Alain Dupuy, Olivier Hermine, Jean-Francois Nicolas, Veronique Latger-Cannard, Daniele Bensoussan, Pierre Bordigoni, Francoise Baleux, Francoise Le Deist, Jean-Louis Virelizier, Fernando Arenzana-Seisdedos, and Francoise Bachelerie*
Unite d'Immunologie Virale, Institut Pasteur, Paris, France
Servicio de Reumatologia, Unidad de Investigacion, Hospital 12 de Octubre, Madrid, Spain
Service d'Anatomie Pathologique, Hopital Saint-Louis, Paris, France
Service de Dermatologie, Hopital Saint-Louis, Paris, France
Centre National de la Recherche Scientifique Unite Mixte de Recherche 8147, Hopital Necker, Paris, France
INSERM U503, Universite Claude Bernard et Hospices Civiles de Lyon, Lyon, France
Service d'Hematologie Biologique, Centre Hospitalo-Universitaire de Nancy, Vandoeuvre-Les-Nancy, France
Service de Therapie Cellulaire et Tissulaire, Centre Hospitalo-Universitaire de Nancy, Vandoeuvre-Les-Nancy, France
Unite de Transplantation Medullaire, Centre Hospitalo-Universitaire de Nancy, Vandoeuvre-Les-Nancy, France
Unite de Chimie Organique, Institut Pasteur, Paris, France
Laboratoire d'Immunologie Pediatrique, Hopital Necker-Enfants Malades, Paris, France
* Corresponding author; email: fbachele{at}pasteur.fr.
The WHIM syndrome is a rare immunodeficiency disorder characterized by Warts, Hypogammaglobulinemia, Infections and Myelokathexis. Dominant heterozygous mutations of the gene encoding CXCR4, a G protein-coupled receptor with a unique ligand, CXCL12, have been associated with this pathology. We studied patients belonging to three different pedigrees. Two siblings inherited a CXCR4 mutation encoding a novel C-terminally truncated receptor. Two unrelated patients were found to bear a wild-type CXCR4 open reading frame. Circulating lymphocytes and neutrophils from all patients displayed similar functional alterations of CXCR4-mediated responses featured by a marked enhancement of G-protein dependent responses. This phenomenon relies on the refractoriness of CXCR4 to be both desensitized and internalized in response to CXCL12. Therefore, the aberrant dysfunction of the CXCR4-mediated signaling constitutes a common biological trait of WHIM syndromes with different causative genetic anomalies. Responses to other chemokines, namely CCL4, CCL5 and CCL21, were preserved, suggesting that in clinical forms associated with a wild-type CXCR4 open reading frame, the genetic anomaly might target an effector with some degree of selectivity for the CXCL12/CXCR4 axis. We propose that the sustained CXCR4 activity in patient cells accounts for the immune-haematological clinical manifestations and the profusion of warts characteristic of the WHIM syndrome.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. Basu and H. E. Broxmeyer
CCR5 Ligands Modulate CXCL12-Induced Chemotaxis, Adhesion, and Akt Phosphorylation of Human Cord Blood CD34+ Cells
J. Immunol.,
December 1, 2009;
183(11):
7478 - 7488.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Crowther-Swanepoel, M. Qureshi, M. J. S. Dyer, E. Matutes, C. Dearden, D. Catovsky, and R. S. Houlston
Genetic variation in CXCR4 and risk of chronic lymphocytic leukemia
Blood,
November 26, 2009;
114(23):
4843 - 4846.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Levoye, K. Balabanian, F. Baleux, F. Bachelerie, and B. Lagane
CXCR7 heterodimerizes with CXCR4 and regulates CXCL12-mediated G protein signaling
Blood,
June 11, 2009;
113(24):
6085 - 6093.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Lazarczyk, P. Cassonnet, C. Pons, Y. Jacob, and M. Favre
The EVER Proteins as a Natural Barrier against Papillomaviruses: a New Insight into the Pathogenesis of Human Papillomavirus Infections
Microbiol. Mol. Biol. Rev.,
June 1, 2009;
73(2):
348 - 370.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Eash, J. M. Means, D. W. White, and D. C. Link
CXCR4 is a key regulator of neutrophil release from the bone marrow under basal and stress granulopoiesis conditions
Blood,
May 7, 2009;
113(19):
4711 - 4719.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Lagane, K. Y. C. Chow, K. Balabanian, A. Levoye, J. Harriague, T. Planchenault, F. Baleux, N. Gunera-Saad, F. Arenzana-Seisdedos, and F. Bachelerie
CXCR4 dimerization and {beta}-arrestin-mediated signaling account for the enhanced chemotaxis to CXCL12 in WHIM syndrome
Blood,
July 1, 2008;
112(1):
34 - 44.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Couturier, C. Sarkis, K. Seron, S. Belouzard, P. Chen, A. Lenain, L. Corset, J. Dam, V. Vauthier, A. Dubart, et al.
Silencing of OB-RGRP in mouse hypothalamic arcuate nucleus increases leptin receptor signaling and prevents diet-induced obesity
PNAS,
December 4, 2007;
104(49):
19476 - 19481.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. K. Kim, M. De La Luz Sierra, C. K. Williams, A. V. Gulino, and G. Tosato
G-CSF down-regulation of CXCR4 expression identified as a mechanism for mobilization of myeloid cells
Blood,
August 1, 2006;
108(3):
812 - 820.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Ueda, N. F. Neel, E. Schutyser, D. Raman, and A. Richmond
Deletion of the COOH-Terminal Domain of CXC Chemokine Receptor 4 Leads to the Down-regulation of Cell-to-Cell Contact, Enhanced Motility and Proliferation in Breast Carcinoma Cells
Cancer Res.,
June 1, 2006;
66(11):
5665 - 5675.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
