From emergency myelopoiesis to chronic myeloid reprogramming: hematopoietic dysregulation in multiple sclerosis

Multiple sclerosis (MS) is classically understood through pathogenic T and B cell responses, while increasing evidence indicates that altered myelopoiesis and bone marrow-derived myeloid programs also contribute to disease initiation and progression. This review summarizes the dynamic evolution of hematopoietic dysregulation in MS, proposing a pathological mechanism spanning from transient emergency myelopoiesis to persistent chronic myeloid reprogramming. Driven by sustained inflammatory stress, hematopoietic stem and progenitor cells (HSPCs) undergo epigenetic remodeling to acquire a stable myeloid differentiation bias. Regulatory crosstalk between the inflamed central nervous system (CNS) and the bone marrow may occur through a neuro bone marrow axis involving anatomical fluid drainage, neuroendocrine and circadian regulation, and immune cell feedback loops. This bone marrow-derived reprogramming modulates the downstream effector functions of myeloid cells following their infiltration into the CNS. This framework may refine stage-matched therapeutic thinking in MS by highlighting maladaptive myelopoiesis and immune-homeostatic modulation as potential intervention targets.