Dopaminergic signalling limits suppressive activity and gut homing of regulatory T cells upon intestinal inflammation

Evidence from inflammatory bowel diseases (IBD) patients and animal models has indicated that gut inflammation is driven by effector CD4(+) T-cell, including Th1 and Th17. Conversely, Treg seem to be dysfunctional in IBD. Importantly, dopamine, which is abundant in the gut mucosa under homoeostasis, undergoes a sharp reduction upon intestinal inflammation. Here we analysed the role of the high-affinity dopamine receptor D3 (DRD3) in gut inflammation. Our results show that Drd3 deficiency confers a stronger immunosuppressive potency to Treg, attenuating inflammatory colitis manifestation in mice. Mechanistic analyses indicated that DRD3-signalling attenuates IL-10 production and limits the acquisition of gut-tropism. Accordingly, the ex vivo transduction of wild-type Treg with a siRNA for Drd3 induced a potent therapeutic effect abolishing gut inflammation. Thus, our findings show DRD3-signalling as a major regulator of Treg upon gut inflammation.

Automated summary

This passage highlights the role of the high-affinity dopamine receptor D3 (DRD3) in regulating immunosuppressive potency of Treg in inflammatory bowel diseases, showing that Drd3 deficiency enhances Treg's immunosuppressive ability and mitigates colitis manifestation. DRD3-signalling attenuates IL-10 production and limits the acquisition of gut-tropism, making it a major regulator of Treg in gut inflammation.