Neonatal lymph node stromal cells drive myelodendritic lineage cells into a distinct population of CX3CR1 (cid:1) CD11b (cid:1) F4/80 (cid:1) regulatory macrophages in mice

Beyond providing a scaffold for immune cells, recent studies indicate that lymph node stromal cells provide potent regulatory capacities that affect the quality of adaptive immune responses. In this study, we provide evidence that neonatal lymph node stromal cells (nnLNSCs) consis-tently promote the differentiation of macrophage dendritic cell progenitors as well as mature and immature dendritic cells into a distinct population of CX3CR1 (cid:1) CD11b (cid:1) F4/80 (cid:1) regulatory macrophages (regM (cid:2) ). These cells possess remarkably low levels of T cell costimulatory molecules as well as MHC class II molecules. regM (cid:2) do not interfere with early T-cell activation but, via nitric oxide secretion, efficiently suppress T-cell proliferation. Furthermore, CD4 (cid:1) T cells proliferating in the presence of regM (cid:2) gain immunosuppressive capacity and M (cid:2) isolated from day 3 nnLNs are T-cell immunosuppres-sive.Adoptive transfer of regM (cid:2) inducesa profound antigen-specific immune suppression in vivo. Together our data show that nnLNSCs skew the differentiation of dendritic cells and their progenitors toward regM (cid:2) , thus revealing a novel mechanism for local immune regulation. ( Blood . 2012;119(17):3975-3986)

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