Distorted expression of dopamine receptor genes in systemic lupus erythematosus

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.