Dopamine receptors are expressed on cells of the immune system, and lack of dopamine has been linked to inflammation in the central nervous system. In Cell, Zhou and colleagues report that dopamine negatively regulates the activation of NLRP3 inflammasomes and thereby prevents the processing and release of interleukin 1β (IL-1β) and IL-18. Dopamine has no effect on AIM2 or NLRC4 inflammasomes. Knockdown or deficiency of the dopamine receptor DRD1 abrogates the dopamine-mediated inhibition of NLRP3; conversely, DRD1 agonists also suppress the activation of NLRP3. Mechanistically, dopamine-DRD1 elicits the production of cAMP, which promotes Lys48-linked polyubiquitination of NLRP3 by the E3 ligase MARCH7. This modification leads to the aggregation of NLRP3 and its subsequent degradation via an autophagic pathway. Dopamine therefore acts as a brake on NLRP3 to limit inflammation.

Cell 160, 62–73 (2015)