Fig. 28

Temporal Differentiation Probabilities in a CCI Patient. Fate probability denotes the predicted likelihood of each cell differentiating into a given terminal subcluster (higher values indicate stronger commitment). “Selected Cells” highlights the target lineage versus “Other Cells.” Across pseudotime, early stages (panels (O, J, E, S, G, L)) show predominant differentiation into monocytes, megakaryocytes/platelets, DC2, pDC, and neutrophils—reflecting a hyperinflammatory response. Mid stages (panels (B, C, F, K, M, N, P)) reveal a shift toward T-cell populations, plasma cells, and CD16⁺ NK cells, indicating a transition from inflammation to repair. Late stages (panels (H, Q)) are characterized by increased B-cell differentiation, marking the onset of antibody-mediated adaptive immunity. Notably, CCL5 expression remains enriched in megakaryocyte/platelet, Tem/Trm cytotoxic T, and CD16⁺ NK clusters throughout, consistent with our model in which Ani HBr sequentially targets ELANE followed by CCL5 to dampen excessive inflammation and promote immune homeostasis.