Emergency myelopoiesis in murine arthritis results in cell-intrinsic changes in dendritic cell development and...

Rheumatoid arthritis affects ∼1% of adult population, results in joint inflammation and systemic comorbidities, and is driven by pathogenic hyperactivation of both innate and adaptive immune systems. We demonstrate that emergency myelopoiesis is induced in rheumatoid arthritis, enhancing innate immune cell production and generating functionally altered innate immune cells. Importantly, these mechanisms impact dendritic cells-antigen-presenting cells that bridge innate and adaptive immune responses. Such effects are intrinsic to hematopoietic stem and progenitor cells (HSPCs) and persist ex vivo independently of inflammatory disease milieu. Dendritic cells derived from HSPCs of arthritis afflicted mice show global changes in gene expression, cytokine production, and induction of activation and checkpoint markers. Furthermore, such dendritic cells have altered capacity for T cell activation. Overall, this characterizes how chronic inflammation and induction of emergency myelopoiesis affect dendritic cell development and function in models of rheumatoid arthritis, with implications for other disorders of chronic inflammation.