Conclusions
T helper 17 cell-derived GM-CSF contributes to DED pathogenesis by promoting CD11b+ cell activation and migration to the ocular surface.
Methods
In a murine model of DED, quantitative real-time PCR and ELISA were used to measure GM-CSF expression at the ocular surface, and flow cytometry was used to enumerate GM-CSF producing Th17 cells. A granulocyte-macrophage colony-stimulating factor neutralizing antibody was used topically in vivo and in an in vitro culture system to evaluate the role of GM-CSF in recruiting and maturing CD11b+ cells. Clinical disease severity was evaluated after topical administration of GM-CSF neutralizing antibody.
Purpose
Growing evidence suggests that granulocyte-macrophage colony-stimulating factor (GM-CSF) contributes to T helper 17 (Th17) cell-associated immunoinflammatory diseases. The purpose of this study was to evaluate the effect of T cell-derived GM-CSF on CD11b+ myeloid cell function in dry eye disease (DED).
Results
In dry eye disease, GM-CSF is significantly upregulated at the ocular surface and the frequency of GM-CSF producing Th17 cells is significantly increased in the draining lymph nodes. In vitro neutralization of GM-CSF from CD4+ T cells derived from DED mice suppresses major histocompatibility complex II expression by CD11b+ cells and CD11b+ cell migration. Topical neutralization of GM-CSF in a murine model of DED suppresses CD11b+ maturation and migration, as well as Th17 cell induction, yielding a reduction in clinical signs of disease. Conclusions: T helper 17 cell-derived GM-CSF contributes to DED pathogenesis by promoting CD11b+ cell activation and migration to the ocular surface.