Identification of a Novel OX40L⁺ Dendritic Cell Subset That Selectively Expands Regulatory T cells

We have previously shown GM-CSF derived bone-marrow dendritic cells (G-BMDCs) can induce the selective expansion of Tregs through the surface-bound molecule OX40L; however, the physiological role of this ex vivo derived DC subset remained to be elucidated. We determined GM-CSF administration to mice induced the generation of in vivo derived OX40L⁺ DCs, phenotypically similar to ex vivo OX40L⁺G-BMDCs, in the spleen, brachial lymph nodes and liver. The generation of OX40L⁺ DCs correlated with increased percentages of functionally suppressive Tregs in the spleen, brachial lymph nodes, and liver of GM-CSF treated mice. DCs from GM-CSF treated mice expanded Tregs in CD4⁺ T-cell co-cultures in an OX40L dependent manner, suggesting OX40L⁺ DCs may play a role in peripheral Treg homeostasis. Furthermore, comparing the transcriptome data of OX40L⁺ DCs to that of all immune cell types revealed OX40L⁺ DCs to be distinct from steady-state immune cells and, microarray analysis of OX40L⁺G-BMDCs and OX40L^-G-BMDCs revealed higher expression of molecules that are associated with tolerogenic phenotype and could play important roles in the function of OX40L⁺ DCs. These findings suggest that OX40L⁺ DCs may represent a unique DC subset induced under inflammatory conditions that may play an essential role in maintaining Treg homeostasis.