A single-cell transcriptomic chemokine response atlas of immune cells 2309949

Abstract Introduction Chemokines are classically recognized for directing immune cell migration, yet accumulating evidence suggests that they also exert broader immunomodulatory effects that remain insufficiently characterized in vivo. Methods To address this gap, we generated a single-cell RNA-sequencing-based chemokine response dictionary by profiling immune cells from mouse lymph nodes following in vivo stimulation with 40 individual chemokines. To evaluate clinical relevance, public patient response datasets and spatial transcriptomic datasets were integrated with our datasets to access association between chemokine activity and disease states. Results Beyond confirming canonical chemotactic effects, chemokine stimulation induced distinct functional programs across immune cell types. For example, CCL8 could induce antigen-presentation-associated programs in B cells. A cell-type-centric perspective uncovered previously unidentified CXCL10-driven chemokine-driven polarization states in migratory dendritic cells that correlated positively with patient response. Integrating chemokine datasets with glioblastoma and normal brain spatial transcriptomics revealed disease-associated chemokine functions, advancing our understanding of chemokine spatial dynamics. Furthermore, incorporating chemokine datasets into our Immune Response Enrichment Analysis (IREA) software enables simultaneous prediction of cytokine and chemokine activities on immune cells based on gene expression data. Conclusion This chemokine response dictionary provides a systematic resource for dissecting chemokine-driven immune functions beyond chemotaxis. By linking chemokine activity to cellular states, spatial context and patient outcomes, this framework offers new opportunities for immunotherapeutic target discovery and response prediction. Funding Source CRI Technology Impact Award (PI: Ang Cui) Topic Categories Cytokines and Chemokines and their Receptors (CCR)