CXCL14  (CXC 趋化因子配体 14)

CXCL14 (也称为乳腺和肾脏表达的趋化因子 (BRAK))，作为非 ELR CXC 趋化因子。CXCL14 对单核细胞显示趋化活性，但对 B 和 T 细胞没有。CXCL14 参与癌症、免疫反应和上皮细胞增殖和迁移。CXCL14 是一种有效的血管生成抑制剂，也显示出抗菌活性。趋化因子 CXCL14 是一种高度保守的稳态趋化因子，在包括脂肪、脑、乳房、子宫颈、肺、肾和皮肤在内的几种正常组织中组成型表达。CXCL14 与感染性和炎症性疾病、血管生成和癌症有关^[1][2]。
在趋化因子中，CXCL14 在哺乳动物中高度保守，小鼠和人类之间只有两个氨基酸差异。CXCL14 具有四个形成二硫键的保守半胱氨酸残基。此外，通常，N 末端的前 22 个氨基酸是强疏水性的，并充当信号肽，在分泌前被切割。与其他趋化因子一样，CXCL14 是一种化学引诱剂，尤其是对单核细胞而言，可诱导树突状细胞 (DC) 的成熟和迁移。然而，在没有前列腺素 E2 (PGE2) 的情况下，与 CXCL14 相关的单核细胞迁移较弱，表明 PGE2 是 CXCL14 相关趋化性所必需的。单核细胞对 CXCL14 和 PGE2 的反应是特异性的，B细胞和T细胞没有任何趋化反应。除单核细胞外，CXCL14 还特异性增加 CD56+ 自然杀伤 (NK) 细胞的趋化性。CXCL14 负责免疫细胞募集和成熟，以及影响上皮细胞运动，有助于在正常上皮层内建立免疫监视。总体而言，CXCL14 负责免疫细胞的浸润、树突状细胞的成熟、主要组织相容性复合物 (MHC)-I 表达的上调和细胞动员。虽然成纤维细胞来源的 CXCL14 具有肿瘤支持作用，但上皮来源的 CXCL14 主要抑制肿瘤进展^[1][2]。

CXCL14 (also known as breast and kidney-expressed chemokine (BRAK)), as a non-ELR CXC chemokine. CXCL14 displays chemotactic activity for monocytes but not for B and T cells. CXCL14 is involved in cancer, immune responses, and epithelial cell proliferation and migration. CXCL14 is a potent inhibitor of angiogenesis, and also shows antimicrobial activity. The chemokine CXCL14 is a highly conserved, homeostatic chemokine which is constitutively expressed in several normal tissues including adipose, brain, breast, cervix, lung, kidney, and skin. CXCL14 is involved in infectious and inflammatory diseases, angiogenesis, and cancer^[1][2].
Among chemokines, CXCL14 is highly conserved in mammals with only two amino acids difference between mice and humans. CXCL14 has four conserved cysteine residues that form disulfide bonds7. Also, in common, the first 22 amino acids of the N-terminus are strongly hydrophobic and act as a signal peptide, which is cleaved prior to secretion. Like other chemokines, CXCL14 is a chemoattractant, especially for monocytes, and induces maturation and migration of dendritic cells (DCs). However, the CXCL14-related migration of monocyte in the absence of prostaglandin E2 (PGE2) is weak, showing that PGE2 is required for CXCL14-related chemotaxis. Responsiveness of monocytes to CXCL14 and PGE2 is specific, and B and T cells do not have any chemotactic response. In addition to monocytes, CXCL14 specifically increases chemotaxis of CD56+ natural killer (NK) cells. Responsible for immune cell recruitment and maturation, as well as impacting epithelial cell motility, CXCL14 contributes to the establishment of immune surveillance within normal epithelial layers. Overall, CXCL14 is responsible for the infiltration of immune cells, maturation of dendritic cells, upregulation of major histocompatibility complex (MHC)-I expression, and cell mobilization. Although fibroblast-derived CXCL14 has a tumor-supportive role, epithelial-derived CXCL14 mainly inhibits tumor progression^[1][2].

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