Tear duct M cells exacerbate allergic conjunctivitis by facilitating germinal-center reactions.

Abstract

The ocular mucosal surface regularly encounters external materials in the air and tear fluids. Microfold (M) cells, specialized epithelial cells for antigen uptake, are present in tear duct-associated lymphoid tissue (TALT) within the nasolacrimal sac; however, their immunological significance is unclear. We generated Krt5-Cre Tnfrsf11a^flox/flox mice, which lack functional M cells in the TALT, as evidenced by the absence of M-cell markers and reduced nanoparticle uptake. M cell deficiency resulted in fewer T follicular helper (Tfh) and germinal center (GC) B cells in the TALT under steady-state conditions. Upon induction of allergic conjunctivitis, control mice exhibited itching and increased Tfh and immunoglobulin E (IgE⁺) GC B cells in the TALT. However, M cell-deficient mice showed ameliorated allergic symptoms with fewer Tfh and IgE⁺ GC B cells. These findings suggest that M cells in TALT contribute to ocular surface immunosurveillance, whereas, upon allergen exposure, they play a critical role in the development of allergic conjunctivitis.