Abstract
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 via 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.
Highlights
The ocular mucosal surface is exposed to potentially harmful foreign antigens, including pathogenic virus and pollen antigens in the air [1]
secretory IgA (S-IgA) is mainly induced in mucosa-associated lymphoid tissue (MALT) composed of one or more lymphoid follicles found in various submucosal membrane sites of the body, such as the gastrointestinal tract nasopharynx, lung, and ocular mucosa [3]
A proportion of lymphoid tissue of the ocular mucosa is situated in the vicinity of the lacrimal sac, which can be found in humans and rodents and is referred to as tear duct associated lymphoid tissue (TALT) [4,5,6,7]
Summary
The ocular mucosal surface is exposed to potentially harmful foreign antigens, including pathogenic virus and pollen antigens in the air [1]. Tears secreted by the lacrimal glands cover the ocular surface to drain the foreign. S-IgA is mainly induced in mucosa-associated lymphoid tissue (MALT) composed of one or more lymphoid follicles found in various submucosal membrane sites of the body, such as the gastrointestinal tract nasopharynx, lung, and ocular mucosa [3]. MALTs are responsible for inducing immune responses against mucosal antigens. A proportion of lymphoid tissue of the ocular mucosa is situated in the vicinity of the lacrimal sac, which can be found in humans and rodents and is referred to as tear duct associated lymphoid tissue (TALT) [4,5,6,7]. TALT shares anatomical features with other MALTs and may play pivotal roles in immune surveillance and S-IgA induction against antigens in the tear fluid
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