Skewing of the population balance of lymphoid and myeloid cells by secreted and intracellular osteopontin

The balance between myeloid and lymphoid populations must be well controlled. Here, we report that a protein, osteopontin (OPN), skews the balance between myeloid and lymphoid populations during pathogenic conditions, such as infection and autoimmunity. Importantly, two OPN isoforms exert distinct effects in shifting the balance through cell type-specific regulation of apoptosis. Intracellular OPN (iOPN) reduces population sizes of myeloid progenitors and myeloid cells, and secreted OPN (sOPN) increases population sizes of lymphoid cells. The total impact of OPN in skewing leukocyte population balance was observed as host sensitivity to early systemic Candida infection and T cell-mediated colitis. This study suggests novel detrimental roles of two OPN isoforms causing the imbalance of leukocyte populations.