Eotaxin-3/CC Chemokine Ligand 26 Is a Functional Ligand for CX3CR1
Eotaxin-3/CC Chemokine Ligand 26 Is a Functional Ligand for CX3CR1
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DOI：
10.4049/jimmunol.0904126
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发表时间：
2010-12-01
影响因子：
4.4
通讯作者：
Yoshie, Osamu
中科院分区：
文献类型：
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作者：
Nakayama, Takashi;Watanabe, Yoshiko;Yoshie, Osamu
Eotaxin-3/CCL26是CCR3的功能性配体，由IL-4 / il -13刺激的血管内皮细胞大量产生。CCL26还作为CCR1、CCR2和CCR5的天然拮抗剂。在这项研究中，我们报道CCL26仍然是CX3CR1的功能性配体，CX3CR1是fractalkine/CX3CL1的受体，由CD16(+) NK细胞，细胞毒性效应CD8(+) T细胞和CD14（低）CD16（高）单核细胞表达。虽然浓度相对较高，但CCL26在表达人CX3CR1而不表达小鼠CX3CR1的小鼠L1.2细胞中诱导钙通量和趋化性，并与CX3CL1竞争与CX3CR1结合。在使用人PBMCs的趋化性实验中，CCL26不仅吸引嗜酸性粒细胞，还吸引CD16(+) NK细胞、CD45RA(+)CD27(-)CD8(+) T细胞和CD14（低）CD16（高）单核细胞。腹腔注射CCL26迅速募集小鼠嗜酸性粒细胞，并将人CD16(+) NK细胞静脉转移到腹腔。il -4刺激的HUVECs产生CCL26，并有效诱导表达CX3CR1的细胞粘附。实时荧光定量PCR结果显示，银屑病皮损中CX3CL1 mRNA持续存在，而CCL26 mRNA不存在，而特应性皮炎皮损中CCL26 mRNA在所有皮损中均存在，而CX3CL1 mRNA仅在约一半皮损中存在。然而，两种疾病的皮肤病变始终含有高水平的CX3CR1 mRNA。因此，在特应性皮炎中，特别是当CX3CL1表达较低时，CCL26可能部分负责表达CX3CR1的细胞募集。总的来说，CCL26是CX3CR1的另一种激动剂，可能在过敏性疾病中发挥双重作用，通过CCR3吸引嗜酸性粒细胞，通过CX3CR1吸引杀伤淋巴细胞和驻留单核细胞。免疫学杂志，2010,18(5):672 - 679。
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. The Journal of Immunology, 2010, 185: 6472-6479.