Astrocyte-intrinsic signaling of chitinase-like protein CHI3L1 drives inflammation and amplifies demyelination in neuromyelitis optica.

ABSTRACT: Neuromyelitis optica (NMO) is an autoimmune disorder characterized by autoantibodies against the astrocyte water channel aquaporin-4 (AQP4) that cause demyelination in the optic nerves and spinal cord. How astrocytopathy leads to myelination deficits remains unclear. Chitinase-3-like protein 1 (CHI3L1, also known as YKL-40) is predominantly secreted by activated astrocytes, serves as a robust NMO biomarker, and plays a role in immune responses, but how it is induced and shapes astrocyte activation in NMO is not well defined. Using ex vivo and in vivo NMO mouse models together with mice with astrocyte-specific CHI3L1 knockout, we demonstrated that CHI3L1 directly contributed to demyelinating lesions elicited by AQP4 autoantibody-activated astrocytes. With complementary in vitro assays and i

SUBMITTER: Xu H 

PROVIDER: S-EPMC12721897 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature