Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Science, Keio University, Tokyo, Japan.
Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitama, Japan.
Front Immunol. 2021 Nov 22;12:779709. doi: 10.3389/fimmu.2021.779709. eCollection 2021.
The ocular mucosal tissues are exposed to potentially harmful foreign antigens in the air and tear fluid. The tear duct-associated lymphoid tissue (TALT) may contribute to immune surveillance in the eye region. Follicle-associated epithelium (FAE) of TALTs is classified as stratified squamous epithelium and consists of squamous epithelial cells arranged in layers on the basement membrane. In contrast, most mucosa-associated lymphoid tissue is covered by a monolayer of epithelium containing microfold (M) cells. Therefore, antigen uptake and the presence of M cells in TALT are not fully understood. The present study found that a small population of FAE cells in the TALT expressed intestinal M-cell markers, namely Sox8, Tnfaip2, GP2, and OPG. This cell population was identified as functional M cells because of their uptake capacity of luminal nanoparticles. In addition, RANKL, which is essential for M-cell differentiation, was expressed by stroma-like cells at the subepithelial region and its receptor RANK by the FAE in the TALT. The administration of RANKL markedly increased the number of Sox8 M cells. In contrast, deficiency in OPG, an endogenous inhibitor of RANKL, increased the number of M cells in the TALT. These data demonstrate that the RANKL-RANK axis is essential for M-cell differentiation in the TALT. Furthermore, immunization eye drops elicited the production of antigen-specific antibodies in tears, which was enhanced by RANKL administration. Thus, TALT M cells play an important role in the immunosurveillance of the eye region.
眼黏膜组织暴露于空气中和泪液中的潜在有害外来抗原中。泪腺相关淋巴组织 (TALT) 可能有助于眼部的免疫监视。TALTs 的滤泡相关上皮 (FAE) 被分类为复层鳞状上皮，由排列在基底膜上的鳞状上皮细胞组成。相比之下，大多数黏膜相关淋巴组织被单层含有微褶皱 (M) 细胞的上皮覆盖。因此，TALT 中的抗原摄取和 M 细胞的存在尚未完全了解。本研究发现，TALT 中的一小部分 FAE 细胞表达肠 M 细胞标志物，即 Sox8、Tnfaip2、GP2 和 OPG。由于这些细胞能够摄取腔纳米颗粒，因此该细胞群体被鉴定为功能性 M 细胞。此外，RANKL 在黏膜下区域的基质样细胞中表达，其受体 RANK 在 TALT 的 FAE 中表达，这对于 M 细胞分化是必不可少的。RANKL 的给药显著增加了 Sox8 M 细胞的数量。相反，RANKL 的内源性抑制剂 OPG 的缺乏增加了 TALT 中的 M 细胞数量。这些数据表明，RANKL-RANK 轴对于 TALT 中的 M 细胞分化是必不可少的。此外，眼部滴眼免疫接种可引起泪液中产生抗原特异性抗体，而 RANKL 的给药可增强这种作用。因此，TALT M 细胞在眼部的免疫监视中发挥重要作用。
