Dual role of Ninjurin-1 in myeloid cell adhesion and inflammation in relapse-remitting EAE.

Nerve Injury-Induced Protein 1 (Ninjurin-1) is an adhesion molecule implicated in inflammation and tissue injury, yet its role in neuroinflammatory diseases such as multiple sclerosis (MS) remains poorly defined. Here, we identify Ninjurin-1 as a marker and regulator of immune activation and CNS infiltration in relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE), a model of relapsing-remitting MS (RRMS). Using flow cytometry, gene-expression profiling, and in vivo peptide blockade, we show that Ninjurin-1 is markedly upregulated on CNS-infiltrating myeloid cells during disease progression. Ninjurin-1+ myeloid cells display both adhesion-related and inflammatory activation features, characterized by increased antigen presentation, cytokine production, and transcriptional enrichment for genes regulating adhesion, migration, and innate immune signaling. Importantly, therapeutic blockade of Ninjurin-1 reduced clinical severity, CNS immune infiltration, and demyelination in RR-EAE. These findings uncover a previously unrecognized role for Ninjurin-1 in myeloid-driven neuroinflammation and support Ninjurin-1 as a candidate therapeutic target for relapsing-remitting MS.