Fig. 9

Mechanisms of CHI3L1 and immune cell pathogenicity in multiple sclerosis. In multiple sclerosis, T-lymphocytes and B-lymphocytes breach the permeable blood–brain barrier and enter the CNS. Interactions between T-lymphocytes, B-lymphocytes, and microglia lead to the release of antibodies and cytokines, including secreted CHI3L1, which can become pathogenic during inflammation. Antibodies may induce vascular damage and CNS inflammation through complement-dependent or antibody-dependent cellular cytotoxicity, mediated by Fc receptors on microglia and macrophages. Autoreactive B-lymphocytes infiltrate the brain, resulting in elevated intrathecal antibody production. The binding of CHI3L1 and antibodies to target cells may directly cause damage or alter cellular function, leading to demyelination. Additionally, secreted CHI3L1 and antibodies can indirectly promote demyelination by activating autoreactive T-lymphocytes, microglia, and macrophages