CCCdb: a comprehensive manually curated database for cell-cell communication in human and mouse

Cell-cell communication (CCC) is central to the organization, function, and plasticity of multicellular life. Advancing experimental technologies and growing insights into complex multicellular systems and disease microenvironments are driving the demand for experimentally validated CCCs that are systematically and manually curated across diverse tissues, phenotypes, and signaling modalities. Here, we present CCCdb (http://www.licpathway.net/cccdb/index.php), a comprehensive, manually curated database of experimentally validated CCCs for human and mouse. A total of 8467 entries were extracted from thousands of publications, each annotated with standardized information on cell types, tissues, and phenotypes. These entries cover 98 tissues, 1132 cell types, and 548 phenotypes, mediated through communication via direct contact, autocrine, paracrine, and endocrine signaling. CCCdb curates experiment-supported CCCs across cellular subtypes, tissue interfaces, and physiological or pathological states. To enhance accessibility and biological interpretability, CCCdb integrates a ReAct-based AI assistant that enables intelligent natural-language queries and intuitive navigation through biological information. We believe that CCCdb will serve as a foundational resource for elucidating the mechanisms by which cells maintain tissue homeostasis and drive disease progression.