Eotaxin-3/CC chemokine ligand 26 is a functional ligand for CX3CR1.
Eotaxin-3/CCL26 is a functional ligand for CCR3 and abundantly produced by IL-4-/IL-13-stimulated vascular endothelial cells. CCL26 also functions as a natural antagonist for CCR1, CCR2, and CCR5. In this study, we report that CCL26 is yet a functional ligand for CX3CR1, the receptor for fractalkine/CX3CL1, which is expressed by CD16(+) NK cells, cytotoxic effector CD8(+) T cells, and CD14(low)CD16(high) monocytes. Albeit at relatively high concentrations, CCL26 induced calcium flux and chemotaxis in mouse L1.2 cells expressing human CX3CR1 but not mouse CX3CR1 and competed with CX3CL1 for binding to CX3CR1. In chemotaxis assays using human PBMCs, CCL26 attracted not only eosinophils but also CD16(+) NK cells, CD45RA(+)CD27(-)CD8(+) T cells, and CD14(low)CD16(high) monocytes. Intraperitoneal injection of CCL26 into mice rapidly recruited mouse eosinophils and intravenously transferred human CD16(+) NK cells into the peritoneal cavity. IL-4-stimulated HUVECs produced CCL26 and efficiently induced adhesion of cells expressing CX3CR1. Real-time PCR showed that skin lesions of psoriasis consistently contained CX3CL1 mRNA but not CCL26 mRNA, whereas those of atopic dermatitis contained CCL26 mRNA in all samples but CX3CL1 mRNA in only about half of the samples. Nevertheless, the skin lesions from both diseases consistently contained CX3CR1 mRNA at high levels. Thus, CCL26 may be partly responsible for the recruitment of cells expressing CX3CR1 in atopic dermatitis particularly when the expression of CX3CL1 is low. Collectively, CCL26 is another agonist for CX3CR1 and may play a dual role in allergic diseases by attracting eosinophils via CCR3 and killer lymphocytes and resident monocytes via CX3CR1.
Nakayama
Takashi
T
Department of Microbiology, Faculty of Medicine and xLife Science Research Institute, Kinki University, Osaka-Sayama, Osaka, Japna.
Watanabe
Yoshiko
Y
Oiso
Naoki
N
Higuchi
Tomonori
T
Shigeta
Akiko
A
Mizuguchi
Nobuyuki
N
Katou
Fuminori
F
Hashimoto
Kenji
K
Kawada
Akira
A
Yoshie
Osamu
O
D000328:Adult; D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D020013:Calcium Signaling / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000819:agonists / Q000378:metabolism* / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D054397:Receptors, CCR3 / Q000378:metabolism / Q000502:physiology; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
C120429:CCL26 protein, human; C515350:CCR3 protein, human; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D008024:Ligands; D054397:Receptors, CCR3; D019707:Receptors, Chemokine