On the contrary, the absence of TLR4 leads rather to an increase in intestinal inflammation in IL-10−/− mice with uncontrolled generation of aberrant IFN-γ- and IL-17-producing (Foxp3+) Tregs and altered control of IEC turnover.163 T-cell TLR4 can negatively regulate activation signals delivered by the T-cell receptor (TCR) through TRIF-dependent MKP3 signaling.164 These findings163,164 imply that essential TLR4 signals from the commensal microbiota help to limit propagation of colitic effector CD4+ T cells, and significantly ameliorate disease course in the context of IL-10 deficiency. This evidence concerns the gene TLR4 and hyperinsulinemic hypoglycemia, familial, 4.