Impaired CXCR4 desensitization in WHIM leukocytes 1 WHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitization to CXCL12 Short title: Impaired CXCR4 desensitization in WHIM leukocytes
نویسندگان
چکیده
1,10 Unité d’Immunologie Virale et Unité de Chimie Organique, Institut Pasteur, 75724 Paris, France. 2 Servicio de Reumatología, Unidad de Investigación, Hospital 12 de Octubre, 28041 Madrid, Spain. 3-4 Service d’anatomie pathologique et de Dermatologie, Hôpital Saint-louis, 75010 Paris, France. Centre National de la Recherche Scientifique Unite Mixte de Recherche 8147, Hôpital Necker, 75743 Paris, France. INSERM U503, Universite Claude Bernard et Hospices Civils de Lyon, 69007 Lyon, France. Service d’Hématologie Biologique, de Thérapie Cellulaire et Tissulaire et Unité de Transplantation médullaire, Centre Hospitalo-Universitaire de Nancy, 54511 Vandoeuvre-Les-Nancy, France. Laboratoire d’Immunologie Pédiatrique, Hôpital Necker-Enfants Malades, 75743 Paris, France.
منابع مشابه
Leukocyte analysis from WHIM syndrome patients reveals a pivotal role for GRK3 in CXCR4 signaling.
Leukocytes from individuals with warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, a rare immunodeficiency, and bearing a wild-type CXCR4 ORF (WHIM(WT)) display impaired CXCR4 internalization and desensitization upon exposure to CXCL12. The resulting enhanced CXCR4-dependent responses, including chemotaxis, probably impair leukocyte trafficking and account for the imm...
متن کاملWHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitization to CXCL12.
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 3 different pedigrees. Two siblings inherited a CXCR4 mutation encoding...
متن کاملCXCR4 dimerization and -arrestin–mediated signaling account for the enhanced chemotaxis to CXCL12 in WHIM syndrome
WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is an immune deficiency linked in many cases to heterozygous mutations causing truncations in the cytoplasmic tail of CXC chemokine receptor 4 (CXCR4). Leukocytes expressing truncated CXCR4 display enhanced responses to the receptor ligand CXCL12, including chemotaxis, which likely impair their trafficking and contribut...
متن کاملImpaired Recruitment of Grk6 and β-Arrestin2 Causes Delayed Internalization and Desensitization of a WHIM Syndrome-Associated CXCR4 Mutant Receptor
WHIM (warts, hypogammaglobulinemia, infections, and myelokatexis) syndrome is a rare immunodeficiency syndrome linked to heterozygous mutations of the chemokine receptor CXCR4 resulting in truncations of its cytoplasmic tail. Leukocytes from patients with WHIM syndrome display impaired CXCR4 internalization and enhanced chemotaxis in response to its unique ligand SDF-1/CXCL12, which likely cont...
متن کاملCHEMOKINES, CYTOKINES, AND INTERLEUKINS CXCR4 dimerization and -arrestin–mediated signaling account for the enhanced chemotaxis to CXCL12 in WHIM syndrome
WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is an immune deficiency linked in many cases to heterozygous mutations causing truncations in the cytoplasmic tail of CXC chemokine receptor 4 (CXCR4). Leukocytes expressing truncated CXCR4 display enhanced responses to the receptor ligand CXCL12, including chemotaxis, which likely impair their trafficking and contribut...
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