The T cell costimulator TL1A is induced by FcγR signaling in human monocytes and dendritic cells

The recently described TL1A/DR3 ligand/receptor pair mediates strong costimulation of Th1 cells. Activation of T and NK cells induces DR3 expression, permitting soluble recombinant TL1A to increase IFN-gamma production and proliferation of these cells. Gut T cells and macrophages express TL1A, especially in Crohn's disease (CD), and there is a strong association between CD and tl1a single nucleotide polymorphisms. Murine studies implicate TUA in gut inflammation. To determine whether professional T cell-activating cells can express TUA, fresh blood monocytes and monocyte-derived dendritic cells were stimulated with various activating ligands, including TLR agonists, IFN-gamma, and immune complexes. Fc gamma R stimulation strongly induced TL1A mRNA in both cell types, which correlated with the detection of TL1A on the cell surface and in cell culture medium. TLR agonists capable of, P inducing IL-6 and TNF-alpha in monocytes and dendrific cells did not induce surface nor soluble TL1A. Furthermore, we demonstrate that TL1A production in monocytes leads to enhancement of T cell responses. The induction of TL1A on APCs via specific pathway stimulation suggests a role for TL1A in Th1 responses to pathogens, and in CD.