DNAM1 and TIGIT balance the T cell response, with low T cell TIGIT expression corresponding to inflammation in psoriatic disease.

Autor:	Jacobs ME; Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Pouw JN; Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Olde Nordkamp MA; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Radstake TRDJ; Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Leijten EFA; Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Boes M; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.; Department of Pediatrics, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Jazyk:	angličtina
Zdroj:	Immunotherapy advances [Immunother Adv] 2020 Nov 25; Vol. 1 (1), pp. ltaa004. Date of Electronic Publication: 2020 Nov 25 (Print Publication: 2021).
DOI:	10.1093/immadv/ltaa004
Abstrakt:	Objectives: Signals at the contact site of antigen-presenting cells (APCs) and T cells help orchestrate the adaptive immune response. CD155 on APCs can interact with the stimulatory receptor DNAM1 or inhibitory receptor TIGIT on T cells. The CD155/DNAM1/TIGIT axis is under extensive investigation as immunotherapy target in inflammatory diseases including cancer, chronic infection and autoimmune diseases. We investigated a possible role for CD155/DNAM1/TIGIT signaling in psoriatic disease. Methods: By flow cytometry, we analyzed peripheral blood mononuclear cells of patients with psoriasis ( n = 20) or psoriatic arthritis ( n = 21), and healthy individuals ( n = 7). We measured CD155, TIGIT, and DNAM1 expression on leukocyte subsets and compared activation-induced cytokine production between CD155-positive and CD155-negative APCs. We assessed the effects of TIGIT and DNAM1 blockade on T cell activation, and related the expression of CD155/DNAM1/TIGIT axis molecules to measures of disease activity. Results: High CD155 expression associates with tumor necrosis factor (TNF) production in myeloid and plasmacytoid dendritic cells (DC). In CD1c+ myeloid DC, activation-induced CD155 expression associates with increased HLA-DR expression. CD8 T cells - but not CD4 T cells - express high levels of TIGIT. DNAM1 blockade decreases T cell pro-inflammatory cytokine production, while TIGIT blockade increased T cell proliferation. Finally, T cell TIGIT expression shows an inverse correlation with inflammation biomarkers in psoriatic disease. Conclusion: CD155 is increased on pro-inflammatory APCs, while the receptors DNAM1 and TIGIT expressed on T cells balance the inflammatory response by T cells. In psoriatic disease, low TIGIT expression on T cells is associated with systemic inflammation. (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Immunology.)
Databáze:	MEDLINE
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