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

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.