Being at the crossroad of blood and immunity, the bone marrow harbors specialized niches supporting the function of hematopoietic stem cells (HSCs) and immune cells. This includes some T-cells subsets such as memory T-cells and regulatory T-cells, which cross-talk with HSCs and regulate their function. Reporting in Cell, Shi et al extended this scenario and described a novel interplay between HSCs and autoreactive T-cells, which has a pathogenic role and a clinical relevance in multiple sclerosis (MS). This autoimmune disease is characterized by demyelinating lesions in the central nervous system, which are initiated by autoreactive T-cells. Upon being activated in the periphery, these T-cells enter the central nervous system where they promote inflammation and recruit neutrophils and monocytes. These myeloid cells further exacerbate the disease as they produce inflammatory factors and reactivate autoreactive T-cells.