FLT3L neutralization reduces dendritic cell numbers, T Cell activation, and salivary gland lymphocyte infiltration in the NOD.H2h4 Sjögren's mouse model.

Abstract

The Feline McDonough sarcoma-like tyrosine kinase 3 (FLT3)/FLT3 ligand (FLT3L) pathway is associated with pathogenesis of several autoimmune diseases, including Sjögren's. Inflammatory signals increase FLT3L levels; FLT3L signaling promotes further inflammation through the differentiation, function, and survival of immune cells, including dendritic cells (DCs), monocytes, and B cells. Patients with Sjögren's have elevated FLT3L levels, increased infiltration of DCs, macrophages, and B cells into salivary glands and tertiary lymphoid structures (TLS). We hypothesized that therapeutically neutralizing FLT3L may reduce inflammatory manifestations in the NOD.H2h4 spontaneous Sjögren's mouse model. Female mice aged 15 to 17 wk, an age at which features of Sjögren's have developed, were administered an anti-mouse FLT3L monoclonal antibody or isotype control for 8 wk. Compared with control, anti-FLT3L antibody treatment significantly reduced free serum FLT3L, splenic DC numbers, T cell activation, and salivary gland TLS (P < 0.05 for all). Neutralizing FLT3L may effectively treat Sjögren's and other FLT3L-associated autoimmune diseases.