TLRs Regulate the Gatekeeping Functions of the Intestinal Follicle-Associated Epithelium1
TLRs Regulate the Gatekeeping Functions of the Intestinal Follicle-Associated Epithelium1
复制标题
TLR 调节肠滤泡相关上皮的把关功能1
作者：
S. Chabot;Jessica S. Wagner;Stephanie A. Farrant;M. Neutra
适应性粘膜免疫的起始发生在有组织的粘膜淋巴组织中，例如小肠的派伊尔集合淋巴结。粘液淋巴滤泡被特化的滤泡相关上皮（FAE）覆盖，FAE含有M细胞，M细胞介导管腔Ag的摄取和跨上皮转运。FAE细胞还产生吸引Ag呈递树突状细胞（DC）的趋化因子。TLR连接先天性和适应性免疫，但它们在调节FAE功能中的可能作用尚不清楚。我们表明TLR 2在FAE和绒毛上皮中都表达，但注射到小鼠肠腔中的肽聚糖或Pam 3Cys激活TLR 2仅导致FAE中的受体重新分布。TLR2激活以剂量依赖性方式增强M细胞对微粒的跨上皮转运。此外，TLR2激活诱导基质金属蛋白酶依赖的迁移到FAE的上皮下树突状细胞，但不进入绒毛上皮的野生型和TLR4缺陷型小鼠。在TLR2缺陷小鼠中未观察到这些反应。因此，派尔集合淋巴结的FAE以不同于绒毛上皮的方式响应TLR2配体。管腔内LPS，一种TLR4配体，也增强了FAE的微粒摄取，并诱导DC迁移到FAE中，这表明其他TLRs可能调节FAE功能。我们的结论是TLR介导的信号调节FAE的守门功能，以促进DC在有组织的粘膜淋巴组织中捕获Ag。
Initiation of adaptive mucosal immunity occurs in organized mucosal lymphoid tissues such as Peyer’s patches of the small intestine. Mucosal lymphoid follicles are covered by a specialized follicle-associated epithelium (FAE) that contains M cells, which mediate uptake and transepithelial transport of luminal Ags. FAE cells also produce chemokines that attract Ag-presenting dendritic cells (DCs). TLRs link innate and adaptive immunity, but their possible role in regulating FAE functions is unknown. We show that TLR2 is expressed in both FAE and villus epithelium, but TLR2 activation by peptidoglycan or Pam3Cys injected into the intestinal lumen of mice resulted in receptor redistribution in the FAE only. TLR2 activation enhanced transepithelial transport of microparticles by M cells in a dose-dependent manner. Furthermore, TLR2 activation induced the matrix metalloproteinase-dependent migration of subepithelial DCs into the FAE, but not into villus epithelium of wild-type and TLR4-deficient mice. These responses were not observed in TLR2-deficient mice. Thus, the FAE of Peyer’s patches responds to TLR2 ligands in a manner that is distinct from the villus epithelium. Intraluminal LPS, a TLR4 ligand, also enhanced microparticle uptake by the FAE and induced DC migration into the FAE, suggesting that other TLRs may modulate FAE functions. We conclude that TLR-mediated signals regulate the gatekeeping functions of the FAE to promote Ag capture by DCs in organized mucosal lymphoid tissues.
登录
查看更多内容
影响因子：
6
作者：
Cario, E;Brown, D;Podolsky, DK
通讯作者：
Podolsky, DK
影响因子：
32.4
作者：
Cook, DN;Prosser, DM;Lira, SA
通讯作者：
Lira, SA
DOI：
10.1165/rcmb.2003-0370oc
发表时间：
2004-06-01
影响因子：
6.4
作者：
Ichiyasu, H;McCormack, JM;Schneeberger, EE
通讯作者：
Schneeberger, EE
影响因子：
5.8
作者：
Eckmann, L;Kagnoff, MF
通讯作者：
Kagnoff, MF
影响因子：
6.4
作者：
Gewirtz, AT;Yu, YM;Peek, RM
通讯作者：
Peek, RM