T-cell-derived cytokines, such as interferon gamma (IFNγ) and tumor necrosis factor alpha (TNF-α), which play significant pathophysiological roles in triggering IBD, have been found to upregulate intestinal epithelial TLR4 expression in vitro.31,43 Changes in the commensal composition in the genetically susceptible host may result in aberrant TLR4 hyperresponsiveness of the intestinal mucosa.44 But receptor upregulation may also reflect functional loss of immune responses. The gene discussed is TNF; the disease is inflammatory bowel disease.