Thyroid cells from normal and autoimmune thyroid glands suppress T lymphocytes proliferation upon contact revealing a new regulatory inhibitory type of interaction independent of PD1/PDL1.

Autor: Álvarez-Sierra D; Translational Immunology Research Group, Vall d'Hebron Institute of Research (VHIR), Campus Vall d'Hebron, Barcelona, Spain; Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain. Electronic address: danielalsie@gmail.com., Sánchez-Gaona N; Translational Immunology Research Group, Vall d'Hebron Institute of Research (VHIR), Campus Vall d'Hebron, Barcelona, Spain., Cruz Cobo M; Translational Immunology Research Group, Vall d'Hebron Institute of Research (VHIR), Campus Vall d'Hebron, Barcelona, Spain., Escriche A; Cellular Plasticity and Cancer Group, Vall d'Hebron Institute of Oncology (VHIO), Campus Vall d'Hebron, Barcelona, Spain., Abad M; Cellular Plasticity and Cancer Group, Vall d'Hebron Institute of Oncology (VHIO), Campus Vall d'Hebron, Barcelona, Spain., Gómez-Brey A; Transplant Coordination Department, Hospital Universitari Vall d'Hebron (HUVH), Campus Vall d'Hebron. Barcelona, Spain., Bello I; Thoracic Surgery and Lung Transplantation Department, Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Campus Vall d'Hebron, Spain., Caubet E; Department of General Surgery, Endocrine Surgery Division, Hospital Universitari Vall d'Hebron (HUVH), Campus Vall d'Hebron, Barcelona, Spain., González Ó; Department of General Surgery, Endocrine Surgery Division, Hospital Universitari Vall d'Hebron (HUVH), Campus Vall d'Hebron, Barcelona, Spain., Zafón C; Department of Endocrinology and Nutrition, Hospital Universitari Vall d'Hebron (HUVH), Campus Vall d'Hebron, Barcelona, Spain., Iglesias C; Department of Histopathology, Hospital Universitari Vall d'Hebron (HUVH), Campus Vall d'Hebron, Barcelona, Spain., Moreno P; Department of General Surgery, Endocrine Surgery Division, Hospital Universitari de Bellvitge (HUB), Barcelona, Spain., Petit A; Department of Histopathology, Hospital Universitari de Bellvitge (HUB), Barcelona, Spain., Fernández-Sanmartín MA; Flow Cytometry Facility, Germans Trias i Pujol Research Institute, Campus Can Ruti, Badalona, Spain., Martínez-Gallo M; Translational Immunology Research Group, Vall d'Hebron Institute of Research (VHIR), Campus Vall d'Hebron, Barcelona, Spain; Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain., Pujol-Borrell R; Translational Immunology Research Group, Vall d'Hebron Institute of Research (VHIR), Campus Vall d'Hebron, Barcelona, Spain; Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain; Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB), Campus Vall d'Hebron, Barcelona, Spain.
Jazyk: angličtina
Zdroj: Journal of autoimmunity [J Autoimmun] 2023 Apr; Vol. 136, pp. 103013. Date of Electronic Publication: 2023 Feb 27.
DOI: 10.1016/j.jaut.2023.103013
Abstrakt: Immune Checkpoint Receptors include a number of inhibitory receptors that limit tissue damage during immune responses; blocking PD-1/PD-L1 checkpoint receptor axis led to a paradigm shift in cancer immunotherapy but also to autoimmune adverse effects, prominently thyroid autoimmunity. Although PD-L1 is known to be expressed on thyroid follicular cells (TFCs) of autoimmune glands the role on PD-1/PD-L1 in the interaction between T cells and thyroid cells in the tissue has not been investigated. Here we report that autologous primary TFCs, but not transformed TFCs, inhibit CD4 and CD8 T cell proliferation but no cytokine production. This effect is not, however, mediated by PD-1/PD-L1 nor locally produced cytokines. Beta galactosidase analysis excluded culture-induced senescence as an explanation. High resolution flow cytometry demonstrated that autologous TFC/T cells co-culture induced the expansion of several clusters of double negative (DN) T cells characterized by high expression of activation markers and negative immune checkpoints. Single cell transcriptomic profiling demonstrated that dissociated TFC express numerous candidate molecules for mediating this suppressive activity, including CD40, E-Cadherin and TIGIT ligands. These ligands directly or through the generation of a suppressor population of DN T cells, and not the PD-1/PD-L1 axis, are most likely the responsible of TFC immunosuppressive activity. These results contribute to reveal the complex network of inhibitory mechanism that operate at the tissue level to restrain autoimmunity but also point to pathways, other that PD-1/PD-L1, that can contribute to tumor evasion.
Competing Interests: Declaration of competing interest No competing financial interests exist.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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