title: TL1A increases expression of CD25, LFA-1, CD134 and CD154, and induces IL-22 and GM-CSF production from effector CD4 T-cells.
abstract: Elevated levels of the cytokine TL1A is associated with several autoimmune diseases e.g. rheumatoid arthritis and inflammatory bowel disease. However, the exact role of TL1A remains elusive. In this study, we investigated the function of TL1A in a pro-inflammatory setting. We show that TL1A together with IL-12, IL-15 and IL-18 increases expression of the co-stimulatory molecules CD154 (CD40 ligand) and CD134 (OX40) on previously activated CD4+ T cells. This indicates that TL1A functions as a co-stimulatory molecule, decreasing the activation threshold of T-cells. We have previously shown that TL1A co-stimulation strongly induces IL-6 in human healthy leukocytes. Interestingly, the cytokine-activated effector T-cells did not produce IL-6 in response to TL1A, indicating distinct effects of TL1A on different cell populations. We further show that this co-stimulation increases the expression of CD25 (IL-2Rα) and CD11a (α-chain of LFA-1) on CD4 T-cells, likely governing increased IL-2/IL-15 sensitivity and cell-cell contact. Along with this, TL1A co-stimulation caused a specific induction of IL-22 and GM-CSF from the activated T-cells. These results substantially contribute to the explanation of TL1A's role in inflammation. Our results suggest that TL1A should be considered as a target for immunotherapeutic treatment of rheumatoid arthritis and inflammatory bowel disease.
authors.affiliation: Section for Experimental Animal Models, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Reichwald
authors.affiliation: Section for Experimental Animal Models, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Tina Z
authors.initials: TZ
authors.lastname: Jørgensen
authors.affiliation: Section for Experimental Animal Models, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Skov
mesh_terms: D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D023201:CD40 Ligand / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis*; D007378:Interleukins / Q000096:biosynthesis*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis*; D053262:Receptors, OX40 / Q000096:biosynthesis*; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000378:metabolism*; D000097043:Interleukin-22
chemical_list: D023201:CD40 Ligand; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D053645:Interleukin-2 Receptor alpha Subunit; D007378:Interleukins; D016169:Lymphocyte Function-Associated Antigen-1; D053262:Receptors, OX40; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D000097043:Interleukin-22; C508017:IL2RA protein, human; C505716:TNFRSF4 protein, human; C117026:TNFSF15 protein, human