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The T Cell Costimulator TL1A Is Induced by FcR Signaling in Human Monocytes and Dendritic Cells

Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California 90048

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- 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-, and immune complexes. FcR 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- 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. Stephan R. Targan, Division of Gastroenterology, Inflammatory Bowel Disease Center, and Immunobiology Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite D4063, Los Angeles CA 90048. E-mail address: targans{at}cshs.org

² Abbreviations used in this paper: DR3, death domain receptor 3; DC, dendritic cell; DcR3, decoy receptor 3; IC, immune complex; MFI, mean fluorescence intensity; Pam₃CSK₄, N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-[R]-Cys-[S]-Ser-[S]-Lys(4) trihydrochloride.

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