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Background: Dopamine is a neurotransmitter and has been found to regulate lymphocytes by acting on dopamine receptors (DRs). CD4 + T cells express all the five subtypes of DRs, D1R to D5R. Although CD4 + T cells have been involved in pathogenesis of rheumatoid arthritis (RA), roles of DRs expressed on these cells in RA are poorly understood. This study determined whether D2R expressed on CD4 + T cells regulates inflammatory responses and signs in collagen type II (CII)-induced arthritis (CIA), a mouse model of RA.

Methods: DBA/1 mice and C57BL/6 mice with global D1r or D2r deficiency (D1r -/- or D2r -/- ) or CD4 + T cell-specific D2r deletion (D2r fl/fl /CD4 Cre ) were used to prepare CIA model by intradermal injection of CII. D2R agonist sumanirole was intraperitoneally administered in CIA mice. CD4 + T cells obtained from CIA mice were exposed to sumanirole or/and D2R antagonist L-741,626 in vitro. Arthritic symptoms were assessed by clinical arthritis scores. Flow cytometric assay measured frequencies of CD4 + T cell subsets (Th1, Th2, Th17 and Treg cells). Expression of specific transcription factors for the CD4 + T cell subsets was tested by Western blot. Cytokine production was estimated by quantitative PCR and ELISA.

Results: CIA mice manifested a bias of CD4 + T cells towards Th1 and Th17 cells. D2r -/- CIA mice showed a stronger bias towards Th1 and Th17 phenotypes than CIA mice, while D1r -/- CIA mice did not show the changes. CD4 + T cell-specific D2r deletion exacerbated both the polarization towards Th1 and Th17 cells and the symptoms of arthritis. Sumanirole administration in CIA mice ameliorated the bias of CD4 + T cells towards Th1 and Th17 phenotypes as well as arthritic symptoms. Sumanirole treatment of in vitro CD4 + T cells obtained from CIA mice promoted the shift to Treg cells, and the effect of sumanirole was blocked by L-741,626.

Conclusions: D2R expressed on CD4 + T cells is protective against imbalance between pro-inflammatory and anti-inflammatory T cells and arthritic symptoms in CIA.

Titel:	Dopamine D2 receptor on CD4 <superscript>+</superscript> T cells is protective against inflammatory responses and signs in a mouse model of rheumatoid arthritis.
Autor/in / Beteiligte Person:	Wang, XQ ; Cai, HH ; Deng, QW ; Chang, YZ ; Peng, YP ; Qiu, YH
Link:	View record at Springer (Volltext)
Zeitschrift:	Arthritis research & therapy, Jg. 25 (2023-05-26), Heft 1, S. 87
Veröffentlichung:	London : BioMed Central, 2003-, 2023
Medientyp:	academicJournal
ISSN:	1478-6362 (electronic)
DOI:	10.1186/s13075-023-03071-1
Schlagwort:	Animals Mice Disease Models, Animal Mice, Inbred C57BL Mice, Inbred DBA T-Lymphocytes, Regulatory metabolism Th17 Cells metabolism Arthritis, Experimental metabolism Arthritis, Rheumatoid drug therapy Receptors, Dopamine D2 metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Arthritis Res Ther] 2023 May 26; Vol. 25 (1), pp. 87. <i>Date of Electronic Publication: </i>2023 May 26. MeSH Terms: Arthritis, Experimental* / metabolism ; Arthritis, Rheumatoid* / drug therapy ; Receptors, Dopamine D2* / metabolism ; Animals ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice, Inbred DBA ; T-Lymphocytes, Regulatory / metabolism ; Th17 Cells / metabolism References: Neuro Endocrinol Lett. 2012;33(6):643-50. (PMID: 23160220) ; Immunobiology. 2015 Mar;220(3):323-30. (PMID: 25468566) ; Mod Rheumatol. 2011 Jun;21(3):260-6. (PMID: 21188452) ; Biomed Res Int. 2015;2015:496759. (PMID: 26693483) ; Rheumatol Int. 2013 Oct;33(10):2597-605. (PMID: 23722874) ; J Neuroimmunol. 2002 Nov;132(1-2):34-40. (PMID: 12417431) ; Rheumatol Int. 2012 Apr;32(4):887-93. (PMID: 21221592) ; Front Immunol. 2019 Mar 12;10:353. (PMID: 30915067) ; Immunobiology. 2013 Jul;218(7):979-83. (PMID: 23266246) ; J Neuroimmune Pharmacol. 2017 Dec;12(4):602-623. (PMID: 28578466) ; J Rheumatol. 1998 Aug;25(8):1466-71. (PMID: 9712085) ; Clin Exp Rheumatol. 2007 Sep-Oct;25(5 Suppl 46):S4-11. (PMID: 17977483) ; Acta Physiol (Oxf). 2016 Jan;216(1):42-89. (PMID: 25728499) ; Curr Neuropharmacol. 2011 Jun;9(2):278-88. (PMID: 22131937) ; Neuroimmunomodulation. 2013;20(1):1-8. (PMID: 23095308) ; Clin Rheumatol. 2018 Oct;37(10):2621-2632. (PMID: 29934747) ; Rheumatol Int. 2012 Sep;32(9):2731-6. (PMID: 21809006) ; Nature. 2013 Feb 7;494(7435):90-4. (PMID: 23242137) ; Int Immunol. 2018 Nov 14;30(12):591-606. (PMID: 30165447) ; Best Pract Res Clin Rheumatol. 2001 Dec;15(5):677-91. (PMID: 11812015) ; Neuro Endocrinol Lett. 2010;31(6):782-91. (PMID: 21196914) ; PLoS One. 2013 Jun 14;8(6):e65860. (PMID: 23799052) ; J Immunol. 2011 Mar 15;186(6):3745-52. (PMID: 21307293) ; Brain Behav Immun. 2021 Nov;98:110-121. (PMID: 34403737) ; Rheumatology (Oxford). 1999 Mar;38(3):214-20. (PMID: 10325659) ; APMIS. 1989 Jul;97(7):575-84. (PMID: 2665798) ; Neuroimmunomodulation. 2001;9(1):23-33. (PMID: 11435749) ; Exp Biol Med (Maywood). 2016 Dec;241(18):2094-2103. (PMID: 27444150) ; Lancet. 2016 Oct 22;388(10055):2023-2038. (PMID: 27156434) ; J Neurosci Methods. 2008 Sep 30;174(2):272-80. (PMID: 18721826) ; Sci Rep. 2022 Apr 8;12(1):5985. (PMID: 35396380) ; Autoimmun Rev. 2007 Nov;7(1):65-70. (PMID: 17967728) ; J Neuroimmune Pharmacol. 2014 Jun;9(3):302-12. (PMID: 24682738) ; Cell Death Dis. 2022 Mar 15;13(3):240. (PMID: 35292659) ; J Immunol. 2006 Jan 15;176(2):848-56. (PMID: 16393968) ; Autoimmun Rev. 2014 Jun;13(6):668-77. (PMID: 24418308) ; J Neuroimmunol. 2005 Dec;169(1-2):161-71. (PMID: 16150496) ; J Neuroimmunol. 1993 Jun;45(1-2):113-9. (PMID: 8392516) ; Eur J Immunol. 2001 Dec;31(12):3504-12. (PMID: 11745370) ; Methods Mol Biol. 2010;602:181-92. (PMID: 20012399) ; J Neuroimmune Pharmacol. 2020 Mar;15(1):114-164. (PMID: 31077015) Contributed Indexing: Keywords: CD4+ T cells; Collagen-induced arthritis; D2r fl/fl /CD4 Cre mice; Dopamine D2 receptor; Rheumatoid arthritis Substance Nomenclature: 0 (Receptors, Dopamine D2) ; 0 (DRD2 protein, mouse) Entry Date(s): Date Created: 20230526 Date Completed: 20230602 Latest Revision: 20230606 Update Code: 20231215 PubMed Central ID: PMC10214709

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Dopamine D2 receptor on CD4 <superscript>+</superscript> T cells is protective against inflammatory responses and signs in a mouse model of rheumatoid arthritis.