title: Distorted expression of dopamine receptor genes in systemic lupus erythematosus.
abstract: Several observations suggest that alterations in the neurotransmitter dopamine and/or its receptors could be associated with the pathophysiology of lupus. We therefore assessed expression of the five dopamine receptor genes in a cohort of patients. We found that all receptors are expressed in lupus peripheral blood cells. We also discovered that dopamine receptor 2 gene (DR2) was underexpressed, and that DR4 was overexpressed in lupus patients, as compared to controls. Cell sorting of peripheral T- and B-lymphocytes disclosed that the altered DR2 and DR4 expressions were borne by T-cells. These distorted expressions of DR2 and DR4 could influence immune functions in lupus through several mechanisms. Since DR2 can be effective in regulating the activation and differentiation of naive CD4⁺ cells by promoting polarization toward regulatory T-cells, the underexpression of DR2 we have observed may account, at least in part, for the reduction of regulatory T-cell function and/or numbers in lupus. In addition to providing novel insight into disease pathogenesis, our findings may have therapeutic implications. Because DR4 can be effective in triggering T-cell quiescence, its overexpression on lupus T cells suggests that inducing quiescence using DR4-specific agonists may represent a useful strategy in the treatment of lupus.
authors.affiliation: HSPH Proteomics Resource, Department of Genetics and Complex Disease, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Mohieddin
authors.initials: M
authors.lastname: Jafari
authors.forename: Ghasem
authors.initials: G
authors.lastname: Ahangari
authors.forename: Mohammad
authors.initials: M
authors.lastname: Saberi
authors.forename: Shahindokht
authors.initials: S
authors.lastname: Samangoui
authors.forename: Raheleh
authors.initials: R
authors.lastname: Torabi
authors.forename: Moncef
authors.initials: M
authors.lastname: Zouali
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011954:Receptors, Dopamine / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology
chemical_list: D020033:Protein Isoforms; D011954:Receptors, Dopamine