The role of GM-CSF in dendritic cell development in vivo (HEM3P.284)

Abstract

Abstract We have earlier demonstrated that CD11b+CD11c+ dendritic cells (DCs) derived ex vivo from bone marrow precursors with GM-CSF (GM-BMDCs) can selectively expand natural Foxp3+ regulatory T-cells (Tregs) in a contact dependent manner through OX40L/Jagged-1 co-signaling. However, an ‘in vivo’ counterpart of these GM-BMDCs is not known. In contrast BMDCs derived ex vivo using FLT3L (FL-BMDCs) are considered to be phenotypical and functional equivalents of physiological steady-state DCs. In addition, mice lacking GM-CSF or its receptor do not show a severe defect in DC development while FLt3L deficiency severely affects the physiological development of all types of DCs. To determine the role of GM-CSF in DC-development in vivo, we treated Flt3L deficient mice with GM-CSF and found no evidence of CD11c+ DC development. In contrast, we saw near complete reconstitution of DCs in these mice with Flt3L treatment. Surprisingly, we could successfully generate CD11c+ GM-BMDCs from bone marrow precursors isolated from these Flt3L deficient mice. Interestingly, these GM-BMDCs also express surface markers associated with precursor cells, macrophages and granulocytes. To address these various contradictions, we propose that G-BMDCs generated ex vivo represent a myeloid precursor population rather than fully differentiated DCs. These ‘precursors’ require other cytokines for their terminal differentiation; thus, Flt3L is critical for their differentiation into steady-state DCs.