CXCL12-CXCR4 chemokine signaling is essential for NK-cell development in adult mice
CXCL12-CXCR4 chemokine signaling is essential for NK-cell development in adult mice
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DOI：
10.1182/blood-2010-04-277897
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发表时间：
2011-01-13
期刊：
影响因子：
20.3
通讯作者：
Nagasawa, Takashi
中科院分区：
文献类型：
--
作者：
Noda, Mamiko;Omatsu, Yoshiki;Nagasawa, Takashi
自然杀伤（NK）细胞是由造血干细胞产生的颗粒淋巴细胞，在抗肿瘤和病毒感染的先天免疫应答中发挥重要作用。已知NK细胞的产生需要几种细胞因子，包括白细胞介素-15（IL-15）和Fms样酪氨酸激酶3配体，但不需要IL-2或IL-7。在这里，我们研究了CXC趋化因子配体-12（CXCL 12）及其主要受体CXCR 4在NK细胞发育中的体内作用。在缺乏CXCL 12或CXCR 4的胚胎中，NK细胞的数量似乎正常;然而，与对照动物相比，成年CXCR 4条件性缺陷小鼠的骨髓、脾脏和外周血中功能性NK细胞的数量严重减少，可能是由于细胞内在CXCR 4缺陷。在培养中，CXCL 12增强了NK细胞从淋巴致敏的多能祖细胞和未成熟NK细胞的产生。在骨髓中，IL-15 mRNA在富含CXCL 12的网状（CAR）细胞中的表达显著高于其他骨髓细胞，并且大多数NK细胞与CAR细胞的突起接触。因此，CXCL 12-CXCR 4趋化因子信号传导对成人NK细胞发育至关重要，CAR细胞可能作为骨髓中NK细胞的生态位发挥作用。（血。2011; 117（2）：451-458）
Natural killer (NK) cells are granular lymphocytes that are generated from hematopoietic stem cells and play vital roles in the innate immune response against tumors and viral infection. Generation of NK cells is known to require several cytokines, including interleukin-15 (IL-15) and Fms-like tyrosine kinase 3 ligand, but not IL-2 or IL-7. Here we investigated the in vivo role of CXC chemokine ligand-12 (CXCL12) and its primary receptor CXCR4 in NK-cell development. The numbers of NK cells appeared normal in embryos lacking CXCL12 or CXCR4; however, the numbers of functional NK cells were severely reduced in the bone marrow, spleen, and peripheral blood from adult CXCR4 conditionally deficient mice compared with control animals, probably resulting from cell-intrinsic CXCR4 deficiency. In culture, CXCL12 enhanced the generation of NK cells from lymphoid-primed multipotent progenitors and immature NK cells. In the bone marrow, expression of IL-15mRNA was considerably higher in CXCL12-abundant reticular (CAR) cells than in other marrow cells, and most NK cells were in contact with the processes of CAR cells. Thus, CXCL12-CXCR4 chemokine signaling is essential for NK-cell development in adults, and CAR cells might function as a niche for NK cells in bone marrow. (Blood. 2011; 117(2):451-458)