Lymphotoxin plays a crucial role in the development and function of nasal-associated lymphoid tissue through regulation of chemokines and peripheral node addressin.
Lymphotoxin plays a crucial role in the development and function of nasal-associated lymphoid tissue through regulation of chemokines and peripheral node addressin.
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淋巴毒素通过趋化因子和外周淋巴结寻址蛋白的调节，在鼻相关淋巴组织的发育和功能中发挥着至关重要的作用。
DOI：
10.1016/s0002-9440(10)62239-0
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Ruddle,NancyH
中科院分区：
文献类型：
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作者：
Ying,Xiaoyan;Chan,Kee;Shenoy,Priti;Hill,Myriam;Ruddle,NancyH
鼻相关淋巴组织（NALT）的发展机制是不完全了解的细胞因子，趋化因子和血管地址素的作用。野生型NALT的发育在出生后立即继续，细胞结构逐渐增加，T细胞区和B细胞区室化，以及光毒素（LT）-α、LT-β和淋巴样趋化因子（CCL 21、CCL 19、CXCL 13）的表达。高内皮微静脉（HEVs）表达GlyCAM-1，HEC-6ST [一种对管腔外周淋巴结地址素（PNAd）表达至关重要的酶]和PNAd本身。LT-β−/−和LT-α−/− NALT的细胞比野生型小鼠少，淋巴趋化因子减少（LT-β−/−）或缺失（LT-α−/−），并且没有T细胞和B细胞区室化。LT-β−/− HEV仅表达近腔PNAd，不表达HEC-6ST或GlyCAM-1。LT-α−/− HEV没有PNAd、HEC-6ST或GlyCAM-1。由于鼻内免疫会产生阴道伊加，因此对保留颈部淋巴结的LT-β−/−小鼠进行免疫可能会产生这种反应。卵清蛋白和霍乱毒素鼻内免疫显示LT-α−/−和LT-β−/− NALT中细胞因子水平较低，阴道伊加检测不到。相比之下，脾脏细胞因子和血清IgG滴度，虽然降低，但可检测到。这些数据表明，LT-α 3和LT-α1β 2通过调节淋巴趋化因子和粘附分子协同促进NALT的发育和功能;它们是第一个暗示LT-α1β 2参与GlyCAM-1在NALT HEV发育中的调节。
The mechanism of nasal-associated lymphoid tissue (NALT) development is incompletely understood with regard to the roles of cytokines, chemokines, and vascular addressins. Development of the wild-type NALT continued in the immediate postnatal period with gradual increases in cellularity, compartmentalization into T- and B-cell zones, and expression of lymphotoxin (LT)-α, LT-β, and lymphoid chemokines (CCL21, CCL19, CXCL13). High endothelial venules (HEVs) developed that expressed GlyCAM-1, HEC-6ST [an enzyme crucial for expression of luminal peripheral node addressin (PNAd)], and PNAd itself. LT-β−/−and LT-α−/−NALTs had fewer cells than those of wild-type mice, reduced (LT-β−/−) or absent (LT-α−/−) lymphoid chemokines, and no T- and B-cell compartmentalization. LT-β−/−HEVs expressed only abluminal PNAd and no HEC-6ST or GlyCAM-1. LT-α−/−HEVs had no PNAd, HEC-6ST, or GlyCAM-1. Because intranasal immunization gives rise to vaginal IgA, immunization of LT-β−/−mice, which retain cervical lymph nodes, might generate such a response. Intranasal immunization with ovalbumin and cholera toxin revealed lower cytokine levels in the LT-α−/−and LT-β−/−NALTs, and undetectable vaginal IgA. In contrast, splenic cytokines and serum IgG titers, although reduced, were detectable. These data indicate that LT-α3and LT-α1β2cooperatively contribute to NALT development and function through regulation of lymphoid chemokines and adhesion molecules; they are the first to implicate LT-α1β2in GlyCAM-1 regulation in NALT HEV development.