Dual Role of Ninjurin-1 in Myeloid Cell Adhesion and Inflammation in Relapse-Remitting EAE

Abstract

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 key mediator 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 a dual function, as both an adhesion molecule and a marker of inflammatory activation, 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 significantly 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 highlight its potential as a therapeutic target for relapsing-remitting MS.