Aggrecan (ACAN) (ACAN)

Aggrecan (ACAN) is a large chondroitin sulfate proteoglycan that is a major structural component of the extracellular matrix in articular cartilage, where it provides the necessary hydration and resistance to compression (UniProt: P16112). In autoimmune conditions such as rheumatoid arthritis and ankylosing spondylitis, aggrecan acts as a critical autoantigen (PubMed: 15546405). The Aggrecan-specific T cell receptor recognition pathway describes the process where dendritic cells (DCs) capture aggrecan, process it into immunogenic peptides (notably from the G1 domain), and present them via MHC class II molecules to specific T-cell receptors (TCRs) (PubMed: 12161505). This interaction triggers the activation of autoreactive CD4+ T cells, leading to a cascade of inflammatory cytokines and cartilage destruction. Therapeutic approaches targeting this pathway focus on inducing antigen-specific tolerance—such as through the use of tolerogenic DCs or peptide vaccines—to silence the pathogenic T-cell response without broad immunosuppression (PubMed: 30361619). Additionally, inhibiting the enzymes responsible for aggrecan degradation, such as ADAMTS-4 and ADAMTS-5, remains a significant area of drug development to preserve joint integrity.

Other names

Aggrecan core proteinCartilage-specific proteoglycan core proteinCSPCPAGC1Proteoglycan 1Chondroitin sulfate proteoglycan 1

Induction of antigen-specific immune tolerance through presentation of aggrecan-derived peptides by tolerogenic dendritic cells to suppress autoreactive T-cell responses; or inhibition of aggrecanases to prevent the release of immunogenic fragments.