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.