title: CXCL14 is a natural inhibitor of the CXCL12-CXCR4 signaling axis.
abstract: Activation of the CXCL12-CXCR4 pathway is crucial for the migration of hematopoietic stem cells, various immune cells, and malignant tumor cells. Here, we show that another CXC chemokine, CXCL14, specifically binds to CXCR4 with high affinity and inhibits the CXCL12-mediated chemotaxis of human leukemia-derived cell lines and CD34(+) hematopoietic progenitor cells. Thus, CXCL14 functions as a natural inhibitor of CXCL12. Our observations suggest that CXCL14 represents, along with CXCR7, molecules that co-evolved with the CXCL12-CXCR4 axis to modulate important physiological processes in development, stem cell maintenance, and immune responses.
authors.affiliation: Stem Cell Project Group, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tanegashima
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Kohei
authors.initials: K
authors.lastname: Tsuji
authors.forename: Akira
authors.initials: A
authors.lastname: Shigenaga
authors.forename: Akira
authors.initials: A
authors.lastname: Otaka
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hara
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism*; D002633:Chemotaxis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D054387:Receptors, CXCR / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity
chemical_list: C118056:CXCL14 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D054387:Receptors, CXCR; D019718:Receptors, CXCR4