Overall, in our model, colonic DA released by ENS dopaminergic neuron or colonic epithelial cells, acting to DRD5 receptor, inhibits M1 but promotes M2 macrophages polarization through the suppression of the NF-κB pathway and activation of the CREB pathway respectively, thereby driving anti-inflammatory protective effects in colitis (Fig. S7). Here, NFKB1 is linked to colitis.