PMC

TGF-β linking the gut microbiota and immune cells. TGF-β is mainly expressed and activated by intestinal epithelial cells (IECs) upon short-chain fatty acid (SCFA) stimulation or by dendritic cells (DCs) after bacterial contact. TGF-β in combination with various cytokines or factors drives the development and/or function of lymphocytes, which reinforce the gut barrier.

TGF-β, secreted under its inactive form due to its association with the Latent Associated Peptide (LAP), is activated by integrin- or metalloproteinase. Activated TGF-β can then bind to TGFβRII, and induce the auto-phosphorylation of TGFβRII, which in turn phosphorylates TGFβRI, leading to the activation of the canonical (SMAD2/3) and non-canonical (ERK, JNK, MAPK, etc.) pathways. Phosphorylated SMAD2/3 form complexes with SMAD4 and translocate into the nucleus to control gene expression, including Smad7, a negative regulator of the canonical pathway. Within the nucleus, SMAD2/3 complexes can be dissociated of SMAD4 by TRIM33, to bind this later and control the expression of similar or different genes.