Ionizing radiation expands a p90RSK-activated patrolling monocyte subset: modulation by colchicine

Background: Ionizing radiation (IR) is known to induce vascular injury and alter immune cell function, yet the molecular mechanisms driving these changes remain incompletely defined. In particular, the role of clonal hematopoiesis-associated proteins expression and stress-responsive signaling pathways in monocyte subsets has not been fully elucidated. Methods: Peripheral blood mononuclear cells (PBMCs) from a single healthy human donor were pre-treated with colchicine and exposed to 2 Gy IR. After 24 h, cells were analyzed using CyTOF with a comprehensive antibody panel targeting lineage markers, DNA damage response proteins, efferocytosis receptors, and clonal hematopoiesis of indeterminate potential (CHIP) associated proteins, including DNMT3A and TET2. Data were processed using the Astrolabe platform to annotate canonical immune subsets. Results: subset. This unique patrolling monocyte population exhibited the highest p90RSK activation and expanded significantly following IR exposure-a response not observed in other monocyte subsets. Colchicine effectively suppressed this IR-induced expansion without restoring DNMT3A or TET2 expression, indicating selective modulation of p90RSK-driven signaling. Conclusion: , supporting a testable hypothesis that colchicine could mitigate vascular inflammation and ultimately reduce cardiovascular risk in cancer survivors.