FIGURE 1.
Graphical overview of the evidence for immune activation in FD. (A) The duodenal immune infiltrate in FD is characterized by increased eosinophil and MC infiltration and degranulation, linked to FD symptoms, neuronal alterations and changes in TJ gene expression. Increased levels of GDNF, IL-6, -1β and iNOS were linked to FD symptoms, TJ gene expression, increased permeability and mast cell degranulation, respectively. (B) Increased CD45RO+ CD45RA+ and gut-homing (α4β7+ CCR9+) lymphocytes were reported in the peripheral circulation of FD patients. In addition, increased anti-CdtB antibodies and hs-CRP, as well as decreased BDNF and MCP-1 were described. (C) Gastric immune alterations in FD include increased EC infiltration and activation, increased MC activation as well as decreased CD206+ macrophage and ICC abundance, although none were linked to symptoms. Increased gastric NGF, GDNF and TRPV1 levels in FD patients were associated to symptoms, along with increased TRPV2, histamine, 5-HT, tryptase and decreased BDNF. Confirmed findings are in bold. Double-headed arrows indicate associations, with confirmed associations in bold. FD: functional dyspepsia, MC: mast cell, TJ: tight junction, GDNF: glial cell-derived neurotrophic factor, iNOS: inducible nitric oxide synthase, CdtB: cytolethal distending toxin B, hs-CRP: high-sensitivity C-reactive protein, BDNF: brain-derived neurotrophic factor, MCP: monocyte chemoattractant protein, EC: enterochromaffin cells, ICC: interstitial cell of Cajal, NGF: nerve growth factor, TRPV: transient receptor potential vanilloid, 5-HT: serotonin. This figure was created in BioRender.