Yuasa Hideto, Mantani Youhei, Masuda Natsumi, Nishida Miho, Arai Masaya, Yokoyama Toshifumi, Tsuruta Hiroki, Kawano Junichi, Hoshi Nobuhiko, Kitagawa Hiroshi
Laboratory of Histophysiology, Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8501, Japan.
Laboratory of Molecular Morphology, Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8501, Japan.
J Vet Med Sci. 2017 Nov 17;79(11):1826-1835. doi: 10.1292/jvms.17-0470. Epub 2017 Oct 8.
The mechanism by which indigenous bacteria on the follicle-associated epithelium (FAE) of lymphatic follicles (LFs) accelerate the differentiation of microvillous columnar epithelial cells (MV) into M-cells was immunohistochemically investigated in rat Peyer's patches. The results showed that the number of Toll-like receptor (TLR) -4 M-cells was greater in the FAE with expansion of bacterial colonies (LFs with bacterial colonies on the FAE: b-LF) than the FAE without expansion of bacterial colonies (nb-LF). TLR-4 was also expressed in the striated borders of MV upstream next to M-cells in the FAE of the b-LF. TLR-4 vesicles were frequently detected in the cytoplasms of MV with TLR-4 striated borders upstream next to TLR-4 M-cells in the FAE of b-LF. These findings suggest that TLR-4 MV take up TLR-4 ligands and differentiate into M-cells in the b-LF. Neither the distribution of RANK nor that of RANKL was coincident with that of M-cells in the b-LF. Moreover, RANK, but not RANKL, was expressed in intestinal villi, whereas cleaved caspase-3 was immunonegative in the MV and M-cells of the FAE, unlike in villous epithelial cells. Therefore, RANK/RANKL signaling in the LF might contribute to the down-regulation of epithelial apoptosis to facilitate the differentiation of MV into M-cells in rat Peyer's patches.
采用免疫组织化学方法,在大鼠派尔集合淋巴结中研究了淋巴滤泡(LF)的滤泡相关上皮(FAE)上的本土细菌加速微绒毛柱状上皮细胞(MV)分化为M细胞的机制。结果显示,与未出现细菌菌落扩张的FAE(无细菌菌落的LF:nb-LF)相比,细菌菌落扩张的FAE(FAE上有细菌菌落的LF:b-LF)中Toll样受体(TLR)-4阳性M细胞数量更多。在b-LF的FAE中,TLR-4也表达于紧邻M细胞上游的MV纹状缘。在b-LF的FAE中,紧邻TLR-4阳性M细胞上游、具有TLR-4纹状缘的MV细胞质中经常检测到TLR-4囊泡。这些发现表明,在b-LF中,TLR-4阳性MV摄取TLR-4配体并分化为M细胞。在b-LF中,RANK和RANKL的分布均与M细胞的分布不一致。此外;RANK在肠绒毛中表达,而RANKL则不表达,与绒毛上皮细胞不同,裂解的半胱天冬酶-3在FAE的MV和M细胞中免疫阴性。因此,LF中的RANK/RANKL信号可能有助于下调上皮细胞凋亡,以促进大鼠派尔集合淋巴结中MV向M细胞的分化。