The T cell costimulator TL1A is induced by FcgammaR 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 TL1A in gut inflammation. To determine whether professional T cell-activating cells can express TL1A, fresh blood monocytes and monocyte-derived dendritic cells were stimulated with various activating ligands, including TLR agonists, IFN-gamma, and immune complexes. FcgammaR 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 inducing IL-6 and TNF-alpha in monocytes and dendritic 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.
Prehn
John L
JL
Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
Thomas
Lisa S
LS
Landers
Carol J
CJ
Yu
Qi T
QT
Michelsen
Kathrin S
KS
Targan
Stephan R
SR
D002462:Cell Membrane / Q000737:chemistry / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008024:Ligands; D009000:Monocytes / Q000737:chemistry / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000819:agonists; D017452:Receptors, IgG / Q000819:agonists / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D008024:Ligands; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D017452:Receptors, IgG; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D007371:Interferon-gamma