Haematopoietic stem and progenitor cells in rheumatoid arthritis.

RA is the prototypic chronic inflammatory disease, characterized by progressive articular cartilage and bone destruction. The systemic nature of RA is evidenced by the increased risk of atherosclerosis and lymphoproliferative disorders. Components of both the innate and adaptive immune system are implicated in the pathophysiology of the articular and extra-articular manifestations of the disease. A fundamental process in the onset of RA is the breakdown in self-tolerance. Accelerated ageing of immune cells (immunosenescence) appears to be a major mechanism favouring the disruption of tolerance. Telomere erosion, a hallmark of immunosenescence, is present in lymphoid (naïve and memory T cells) and myeloid (granulocytes) cells in RA. The premature ageing process also involves the haematopoietic stem and progenitor cells (CD34(+) HSPC), thus extending the RA immunopathogenesis to include early events in the shaping of the immune system. This review summarizes current concepts of HSPC ageing and its impact on immune regeneration, highlighting the phenotypic and functional similarities between elderly and RA HSPC.