PMID- 28360196
OWN - NLM
STAT- MEDLINE
DCOM- 20170918
LR  - 20220419
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 31
IP  - 7
DP  - 2017 Jul
TI  - Epithelial chemokine CXCL14 synergizes with CXCL12 via allosteric modulation of 
      CXCR4.
PG  - 3084-3097
LID - 10.1096/fj.201700013R [doi]
AB  - The chemokine receptor, CXC chemokine receptor 4 (CXCR4), is selective for CXC 
      chemokine ligand 12 (CXCL12), is broadly expressed in blood and tissue cells, and 
      is essential during embryogenesis and hematopoiesis. CXCL14 is a homeostatic 
      chemokine with unknown receptor selectivity and preferential expression in 
      peripheral tissues. Here, we demonstrate that CXCL14 synergized with CXCL12 in 
      the induction of chemokine responses in primary human lymphoid cells and cell 
      lines that express CXCR4. Combining subactive concentrations of CXCL12 with 
      100-300 nM CXCL14 resulted in chemotaxis responses that exceeded maximal 
      responses that were obtained with CXCL12 alone. CXCL14 did not activate 
      CXCR4-expressing cells (i.e., failed to trigger chemotaxis and Ca(2+) 
      mobilization, as well as signaling via ERK1/2 and the small GTPase Rac1); 
      however, CXCL14 bound to CXCR4 with high affinity, induced redistribution of 
      cell-surface CXCR4, and enhanced HIV-1 infection by >3-fold. We postulate that 
      CXCL14 is a positive allosteric modulator of CXCR4 that enhances the potency of 
      CXCR4 ligands. Our findings provide new insights that will inform the development 
      of novel therapeutics that target CXCR4 in a range of diseases, including cancer, 
      autoimmunity, and HIV.-Collins, P. J., McCully, M. L., Martinez-Munoz, L., 
      Santiago, C., Wheeldon, J., Caucheteux, S., Thelen, S., Cecchinato, V., Laufer, 
      J. M., Purvanov, V., Monneau, Y. R., Lortat-Jacob, H., Legler, D. F., Uguccioni, 
      M., Thelen, M., Piguet, V., Mellado, M., Moser, B. Epithelial chemokine CXCL14 
      synergizes with CXCL12 via allosteric modulation of CXCR4.
CI  - (c) The Author(s).
FAU - Collins, Paul J
AU  - Collins PJ
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, United Kingdom.
FAU - McCully, Michelle L
AU  - McCully ML
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, United Kingdom.
FAU - Martinez-Munoz, Laura
AU  - Martinez-Munoz L
AD  - Department Immunology and Oncology, Centro Nacional de Biotecnologia/Consejo 
      Superior de Investigaciones Cientificas, Madrid, Spain.
FAU - Santiago, Cesar
AU  - Santiago C
AD  - Department Immunology and Oncology, Centro Nacional de Biotecnologia/Consejo 
      Superior de Investigaciones Cientificas, Madrid, Spain.
FAU - Wheeldon, James
AU  - Wheeldon J
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, United Kingdom.
FAU - Caucheteux, Stephan
AU  - Caucheteux S
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, United Kingdom.
FAU - Thelen, Sylvia
AU  - Thelen S
AD  - Institute for Research in Biomedicine, Universita della Svizzera Italiana, 
      Bellinzona, Switzerland.
FAU - Cecchinato, Valentina
AU  - Cecchinato V
AD  - Institute for Research in Biomedicine, Universita della Svizzera Italiana, 
      Bellinzona, Switzerland.
FAU - Laufer, Julia M
AU  - Laufer JM
AD  - Biotechnology Institute Thurgau at the University of Konstanz, Kreuzlingen, 
      Switzerland.
AD  - Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, 
      Germany.
FAU - Purvanov, Vladimir
AU  - Purvanov V
AD  - Biotechnology Institute Thurgau at the University of Konstanz, Kreuzlingen, 
      Switzerland.
AD  - Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, 
      Germany.
FAU - Monneau, Yoan R
AU  - Monneau YR
AD  - Institute de Biologie Structurale, Unite Mixtes de Recherche 5075, University 
      Grenoble Alpes, Centre National de la Recherche Scientifique, Commissariat a 
      l'Energie Atomique, Grenoble, France.
FAU - Lortat-Jacob, Hugues
AU  - Lortat-Jacob H
AD  - Institute de Biologie Structurale, Unite Mixtes de Recherche 5075, University 
      Grenoble Alpes, Centre National de la Recherche Scientifique, Commissariat a 
      l'Energie Atomique, Grenoble, France.
FAU - Legler, Daniel F
AU  - Legler DF
AD  - Biotechnology Institute Thurgau at the University of Konstanz, Kreuzlingen, 
      Switzerland.
AD  - Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, 
      Germany.
FAU - Uguccioni, Mariagrazia
AU  - Uguccioni M
AD  - Institute for Research in Biomedicine, Universita della Svizzera Italiana, 
      Bellinzona, Switzerland.
AD  - Department of Medical Biotechnology and Translational Medicine, University of 
      Milan, Milan, Italy.
FAU - Thelen, Marcus
AU  - Thelen M
AD  - Institute for Research in Biomedicine, Universita della Svizzera Italiana, 
      Bellinzona, Switzerland.
FAU - Piguet, Vincent
AU  - Piguet V
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, United Kingdom.
FAU - Mellado, Mario
AU  - Mellado M
AD  - Department Immunology and Oncology, Centro Nacional de Biotecnologia/Consejo 
      Superior de Investigaciones Cientificas, Madrid, Spain.
FAU - Moser, Bernhard
AU  - Moser B
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, United Kingdom; moserb@cardiff.ac.uk.
LA  - eng
GR  - 169936/SNSF_/Swiss National Science Foundation/Switzerland
GR  - MR/L018284/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170330
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (CXCL12 protein, human)
RN  - 0 (CXCL14 protein, human)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Chemokines, CXC)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CXCR4)
SB  - IM
MH  - Amino Acid Sequence
MH  - Cells, Cultured
MH  - Chemokine CXCL12/genetics/*metabolism
MH  - Chemokines, CXC/genetics/*metabolism
MH  - Chemotaxis
MH  - Gene Expression Regulation/*physiology
MH  - HIV-1/physiology
MH  - Humans
MH  - Leukocytes, Mononuclear/*metabolism
MH  - Protein Binding
MH  - Protein Conformation
MH  - RNA, Messenger
MH  - Receptors, CXCR4/genetics/*metabolism
MH  - Signal Transduction
PMC - PMC5472405
OTO - NOTNLM
OT  - CXCR4
OT  - allosteric receptor modulation
OT  - signal transduction
OT  - synergism
EDAT- 2017/04/01 06:00
MHDA- 2017/09/19 06:00
PMCR- 2017/03/30
CRDT- 2017/04/01 06:00
PHST- 2017/01/06 00:00 [received]
PHST- 2017/03/13 00:00 [accepted]
PHST- 2017/04/01 06:00 [pubmed]
PHST- 2017/09/19 06:00 [medline]
PHST- 2017/04/01 06:00 [entrez]
PHST- 2017/03/30 00:00 [pmc-release]
AID - fj.201700013R [pii]
AID - FJ_201700013R [pii]
AID - 10.1096/fj.201700013R [doi]
PST - ppublish
SO  - FASEB J. 2017 Jul;31(7):3084-3097. doi: 10.1096/fj.201700013R. Epub 2017 Mar 30.