The Roslin Institute and the Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Edinburgh, UK.
Mucosal Immunol. 2013 Sep;6(5):1027-37. doi: 10.1038/mi.2012.141. Epub 2013 Jan 30.
The transcytosis of antigens across the follicle-associated epithelium (FAE) of Peyer's patches by microfold cells (M cells) is important for the induction of efficient immune responses to mucosal antigens. The mucosal immune response is compromised by ageing, but effects on M cells were unknown. We show that M-cell density in the FAE of aged mice was dramatically reduced. As a consequence, aged Peyer's patches were significantly deficient in their ability to transcytose particulate lumenal antigen across the FAE. Ageing specifically impaired the expression of Spi-B and the downstream functional maturation of M cells. Ageing also dramatically impaired C-C motif chemokine ligand 20 expression by the FAE. As a consequence, fewer B cells were attracted towards the FAE, potentially reducing their ability to promote M-cell maturation. Our study demonstrates that ageing dramatically impedes the functional maturation of M cells, revealing an important ageing-related defect in the mucosal immune system's ability to sample lumenal antigens.
微皱褶细胞 (M 细胞) 将抗原穿过派尔集合淋巴结的滤泡相关上皮 (FAE) 的转胞吞作用对于诱导黏膜抗原的有效免疫反应很重要。黏膜免疫反应随着年龄的增长而受损,但对 M 细胞的影响尚不清楚。我们发现,老年小鼠 FAE 中的 M 细胞密度显著降低。因此,老年派尔集合淋巴结在将颗粒状腔腔抗原穿过 FAE 转胞吞的能力上存在显著缺陷。衰老特异性地损害了 Spi-B 的表达和 M 细胞的下游功能成熟。衰老还严重损害了 FAE 中 C-C 基序趋化因子配体 20 的表达。结果,较少的 B 细胞被吸引到 FAE,可能降低了它们促进 M 细胞成熟的能力。我们的研究表明,衰老显著阻碍了 M 细胞的功能成熟,揭示了黏膜免疫系统取样腔腔抗原的能力与衰老相关的重要缺陷。