SHIP-1 Modulation in Experimental Allergic Conjunctivitis: Impact on CD4+ T Cell Migration.

PURPOSE: This study aimed to elucidate the role of Src-homology 2 domain-containing inositol-5-phosphatase 1 (SHIP-1) in modulating immune responses in experimental allergic conjunctivitis (EAC) and to assess its therapeutic potential.

METHODS

A short ragweed (SRW)-induced EAC mouse model was treated with subconjunctival injections of the SHIP-1 activator AQX1125 (3 mM/5 μL/eye) or antagonist 3AC (0.2292 μmol/5 μL/eye) every other day. Clinical symptoms were scored periodically, and conjunctival tissues were collected on days 1, 7, and 14 for histopathological (H&E staining) and immunofluorescence analyses. Protein expression in ocular tissues was evaluated by Western blotting, and immune cell profiles in the spleen were characterized by flow cytometry.

RESULTS

Compared to 3AC, AQX1125 markedly attenuated ocular symptoms and reduced disease duration. Histopathological evaluation revealed diminished inflammatory cell infiltration in AQX1125-treated mice, whereas 3AC exacerbated infiltration. Immunofluorescence demonstrated reduced CD4+ T cell recruitment and enhanced SHIP-1 expression in the AQX1125 group at days 7 and 14. Western blot analysis showed upregulation of CCR7 alongside downregulation of PIP3, p-AKT, and p-mTOR in AQX1125-treated mice, while 3AC exerted opposing effects. Additionally, 3AC increased splenic CD4+ T cell populations at days 7 and 14 post-treatment.

CONCLUSION

SHIP-1 activation may represent a promising therapeutic approach for EAC, potentially through suppression of pathogenic CD4+ T cell migration and modulation of the PI3K/AKT/mTOR signaling pathway. These findings underscore the anti-inflammatory properties of SHIP-1 activators in allergic conjunctivitis.