PMID- 30954278 OWN - NLM STAT- MEDLINE DCOM- 20200330 LR - 20200330 IS - 1872-8421 (Electronic) IS - 0165-5728 (Linking) VI - 332 DP - 2019 Jul 15 TI - Dopamine inhibits human CD8+ Treg function through D(1)-like dopaminergic receptors. PG - 233-241 LID - S0165-5728(18)30578-2 [pii] LID - 10.1016/j.jneuroim.2019.02.007 [doi] AB - CD8+ T regulatory/suppressor cells (Treg) affect peripheral tolerance and may be involved in autoimmune diseases as well as in cancer. In view of our previous data showing the ability of DA to affect adaptive immune responses, we investigated the dopaminergic phenotype of human CD8+ Treg as well as the ability of DA to affect their generation and activity. Results show that CD8+ T cells express both D(1)-like and D(2)-like dopaminergic receptors (DR), tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of DA, and vesicular monoamine transporter (VMAT) 2 and contain high levels of intracellular DA. Preferential upregulation of DR mRNA levels in the CD8+CD28- T cell compartment occurs during generation of CD8+ Treg, which is reduced by DA and by the D(1)-like DR agonist SKF-38393. DA and SKF-38393 also reduce the suppressive activity of CD8+ Treg on human peripheral blood mononuclear cells. Treg are crucial for tumor escape from the host immune system, thus the ability of DA to inhibits Treg function supports dopaminergic pathways as a druggable targets to develop original and innovative antitumor strategies. CI - Copyright (c) 2019. Published by Elsevier B.V. FAU - Nasi, Giorgia AU - Nasi G AD - Center of Excellence for Biomedical Research/Department of Internal Medicine, Clinical Immunology Unit, Clinical Immunology Unit, University of Genoa, Genoa, Italy; Biotherapy Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address: gfilaci@unige.it. FAU - Ahmed, Tanzeel AU - Ahmed T AD - Center for Research in Medical Pharmacology, University of Insubria, Varese, Italy. FAU - Rasini, Emanuela AU - Rasini E AD - Center for Research in Medical Pharmacology, University of Insubria, Varese, Italy. FAU - Fenoglio, Daniela AU - Fenoglio D AD - Center of Excellence for Biomedical Research/Department of Internal Medicine, Clinical Immunology Unit, Clinical Immunology Unit, University of Genoa, Genoa, Italy; Biotherapy Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. FAU - Marino, Franca AU - Marino F AD - Center for Research in Medical Pharmacology, University of Insubria, Varese, Italy. Electronic address: franca.marino@uninsubria.it. FAU - Filaci, Gilberto AU - Filaci G AD - Center of Excellence for Biomedical Research/Department of Internal Medicine, Clinical Immunology Unit, Clinical Immunology Unit, University of Genoa, Genoa, Italy; Biotherapy Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. FAU - Cosentino, Marco AU - Cosentino M AD - Center for Research in Medical Pharmacology, University of Insubria, Varese, Italy. Electronic address: franca.marino@uninsubria.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190309 PL - Netherlands TA - J Neuroimmunol JT - Journal of neuroimmunology JID - 8109498 RN - 0 (RNA, Messenger) RN - 0 (Receptors, Dopamine D1) RN - 0 (SLC18A2 protein, human) RN - 0 (Vesicular Monoamine Transport Proteins) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Dopamine/*pharmacology MH - Flow Cytometry MH - Humans MH - Neuroimmunomodulation/physiology MH - RNA, Messenger/biosynthesis MH - Receptors, Dopamine D1/analysis/biosynthesis/*drug effects/genetics MH - T-Lymphocytes, Regulatory/*drug effects/metabolism MH - Tyrosine 3-Monooxygenase/biosynthesis/genetics MH - Vesicular Monoamine Transport Proteins/biosynthesis/genetics OTO - NOTNLM OT - CD8+ Treg OT - Dopamine OT - Dopaminergic receptor EDAT- 2019/04/08 06:00 MHDA- 2020/03/31 06:00 CRDT- 2019/04/08 06:00 PHST- 2018/12/19 00:00 [received] PHST- 2019/02/06 00:00 [revised] PHST- 2019/02/15 00:00 [accepted] PHST- 2019/04/08 06:00 [pubmed] PHST- 2020/03/31 06:00 [medline] PHST- 2019/04/08 06:00 [entrez] AID - S0165-5728(18)30578-2 [pii] AID - 10.1016/j.jneuroim.2019.02.007 [doi] PST - ppublish SO - J Neuroimmunol. 2019 Jul 15;332:233-241. doi: 10.1016/j.jneuroim.2019.02.007. Epub 2019 Mar 9.