PMID- 33512478
OWN - NLM
STAT- MEDLINE
DCOM- 20211207
LR  - 20211214
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 137
IP  - 20
DP  - 2021 May 20
TI  - CXCR4 signaling controls dendritic cell location and activation at steady state 
      and in inflammation.
PG  - 2770-2784
LID - 10.1182/blood.2020006675 [doi]
AB  - Dendritic cells (DCs) encompass several cell subsets that collaborate to initiate 
      and regulate immune responses. Proper DC localization determines their function 
      and requires the tightly controlled action of chemokine receptors. All DC subsets 
      express CXCR4, but the genuine contribution of this receptor to their biology has 
      been overlooked. We addressed this question using natural CXCR4 mutants resistant 
      to CXCL12-induced desensitization and harboring a gain of function that cause the 
      warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS), 
      a rare immunodeficiency associated with high susceptibility to the pathogenesis 
      of human papillomavirus (HPV). We report a reduction in the number of circulating 
      plasmacytoid DCs (pDCs) in WHIM patients, whereas that of conventional DCs is 
      preserved. This pattern was reproduced in an original mouse model of WS, enabling 
      us to show that the circulating pDC defect can be corrected upon CXCR4 blockade 
      and that pDC differentiation and function are preserved, despite CXCR4 
      dysfunction. We further identified proper CXCR4 signaling as a critical 
      checkpoint for Langerhans cell and DC migration from the skin to lymph nodes, 
      with corollary alterations of their activation state and tissue inflammation in a 
      model of HPV-induced dysplasia. Beyond providing new hypotheses to explain the 
      susceptibility of WHIM patients to HPV pathogenesis, this study shows that proper 
      CXCR4 signaling establishes a migration threshold that controls DC egress from 
      CXCL12-containing environments and highlights the critical and subset-specific 
      contribution of CXCR4 signal termination to DC biology.
CI  - (c) 2021 by The American Society of Hematology.
FAU - Gallego, Carmen
AU  - Gallego C
AUID- ORCID: 0000-0003-0180-5671
AD  - Universite Paris-Saclay, INSERM, Inflammation, Microbiome and Immunosurveillance, 
      Clamart, France.
FAU - Vetillard, Mathias
AU  - Vetillard M
AUID- ORCID: 0000-0001-5503-4900
AD  - Universite Paris-Saclay, INSERM, Inflammation, Microbiome and Immunosurveillance, 
      Clamart, France.
FAU - Calmette, Joseph
AU  - Calmette J
AD  - Universite Paris-Saclay, INSERM, Inflammation, Microbiome and Immunosurveillance, 
      Clamart, France.
FAU - Roriz, Melanie
AU  - Roriz M
AD  - Universite Paris-Saclay, INSERM, Inflammation, Microbiome and Immunosurveillance, 
      Clamart, France.
FAU - Marin-Esteban, Viviana
AU  - Marin-Esteban V
AD  - Universite Paris-Saclay, INSERM, Inflammation, Microbiome and Immunosurveillance, 
      Clamart, France.
FAU - Evrard, Maximilien
AU  - Evrard M
AUID- ORCID: 0000-0002-2105-1160
AD  - Singapore Immunology Network (SIgN), Agency for Science, Technology and Research 
      (A*STAR), Biopolis, Singapore-School of Biological Sciences, Nanyang 
      Technological University, Singapore.
FAU - Aknin, Marie-Laure
AU  - Aknin ML
AD  - Ingenierie et Plateformes au Service de l'Innovation Therapeutique (IPSIT) 
      Structure Federative de Recherche-Unite Mixte de Service (SFR-UMS), 
      Chatenay-Malabry, France.
FAU - Pionnier, Nicolas
AU  - Pionnier N
AUID- ORCID: 0000-0002-2379-4945
AD  - Universite Paris-Saclay, INSERM, Inflammation, Microbiome and Immunosurveillance, 
      Clamart, France.
FAU - Lefrancois, Manon
AU  - Lefrancois M
AD  - Universite Paris-Saclay, INSERM, Inflammation, Microbiome and Immunosurveillance, 
      Clamart, France.
FAU - Mercier-Nome, Francoise
AU  - Mercier-Nome F
AD  - Ingenierie et Plateformes au Service de l'Innovation Therapeutique (IPSIT) 
      Structure Federative de Recherche-Unite Mixte de Service (SFR-UMS), 
      Chatenay-Malabry, France.
FAU - Bertrand, Yves
AU  - Bertrand Y
AD  - Institut d'Hematologie et Oncologie Pediatrique-Hematologie et Immunologie 
      Pediatrique, Hopitaux Civils de Lyon, Lyon, France.
FAU - Suarez, Felipe
AU  - Suarez F
AUID- ORCID: 0000-0002-3537-9052
AD  - Laboratory of Molecular Mechanisms of Hematological Disorders and Therapeutic 
      Implications, Imagine Paris, Paris, France.
FAU - Donadieu, Jean
AU  - Donadieu J
AUID- ORCID: 0000-0002-4485-146X
AD  - Service d'Hematologie-Immuno-Oncologie Pediatrique Registre des Neutropenies 
      Assistance Publique-Hopitaux de Paris (AP-HP), Hopital d'Enfants Armand 
      Trousseau, Paris, France.
AD  - Sorbonne Universite, INSERM, Centre de Recherche Saint-Antoine, Centre de 
      Recherche Saint-Antoine (CRSA), Paris, France; and.
FAU - Ng, Lai Guan
AU  - Ng LG
AD  - Singapore Immunology Network (SIgN), Agency for Science, Technology and Research 
      (A*STAR), Biopolis, Singapore-School of Biological Sciences, Nanyang 
      Technological University, Singapore.
FAU - Balabanian, Karl
AU  - Balabanian K
AUID- ORCID: 0000-0002-0534-3198
AD  - Universite Paris-Saclay, INSERM, Inflammation, Microbiome and Immunosurveillance, 
      Clamart, France.
AD  - Universite de Paris, Institut de Recherche Saint-Louis, EMiLy, INSERM, Paris, 
      France.
FAU - Bachelerie, Francoise
AU  - Bachelerie F
AD  - Universite Paris-Saclay, INSERM, Inflammation, Microbiome and Immunosurveillance, 
      Clamart, France.
FAU - Schlecht-Louf, Geraldine
AU  - Schlecht-Louf G
AUID- ORCID: 0000-0002-7924-5371
AD  - Universite Paris-Saclay, INSERM, Inflammation, Microbiome and Immunosurveillance, 
      Clamart, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Benzylamines)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Cxcl12 protein, mouse)
RN  - 0 (Cyclams)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (Recombinant Proteins)
RN  - S915P5499N (plerixafor)
RN  - WHIM syndrome
SB  - IM
CIN - Blood. 2021 May 20;137(20):2716-2717. PMID: 34014296
MH  - Alphapapillomavirus/genetics
MH  - Animals
MH  - Benzylamines/pharmacology
MH  - Cell Count
MH  - Cell Differentiation
MH  - Chemokine CXCL12/physiology
MH  - Chemotaxis
MH  - Cyclams/pharmacology
MH  - Dendritic Cells/classification/*physiology
MH  - Epidermis/pathology
MH  - Female
MH  - Gene Knock-In Techniques
MH  - Genes, Viral
MH  - Humans
MH  - Inflammation/metabolism/*pathology
MH  - Langerhans Cells/physiology
MH  - Lymphoid Tissue/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred Strains
MH  - Mice, Transgenic
MH  - Organ Specificity
MH  - Parabiosis
MH  - Primary Immunodeficiency Diseases/blood/genetics/pathology/*physiopathology
MH  - Receptors, CXCR4/*physiology
MH  - Recombinant Proteins/metabolism
MH  - Warts/blood/genetics/pathology/*physiopathology
EDAT- 2021/01/30 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/01/29 12:13
PHST- 2020/04/29 00:00 [received]
PHST- 2020/12/20 00:00 [accepted]
PHST- 2021/01/30 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/01/29 12:13 [entrez]
AID - S0006-4971(21)00178-6 [pii]
AID - 10.1182/blood.2020006675 [doi]
PST - ppublish
SO  - Blood. 2021 May 20;137(20):2770-2784. doi: 10.1182/blood.2020006675.