TY - JOUR
T1 - Dopaminergic signalling limits suppressive activity and gut homing of regulatory T cells upon intestinal inflammation
AU - Ugalde, Valentina
AU - Contreras, Francisco
AU - Prado, Carolina
AU - Chovar, Ornella
AU - Espinoza, Alexandra
AU - Pacheco, Rodrigo
N1 - Publisher Copyright:
© 2020, Society for Mucosal Immunology.
PY - 2021/5
Y1 - 2021/5
N2 - 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. [Figure not available: see fulltext.]
AB - 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. [Figure not available: see fulltext.]
UR - http://www.scopus.com/inward/record.url?scp=85095980327&partnerID=8YFLogxK
U2 - 10.1038/s41385-020-00354-7
DO - 10.1038/s41385-020-00354-7
M3 - Article
C2 - 33184477
AN - SCOPUS:85095980327
SN - 1933-0219
VL - 14
SP - 652
EP - 666
JO - Mucosal Immunology
JF - Mucosal Immunology
IS - 3
ER -