Figure 10.

A proposed model of circadian clock function in the regenerating small intestinal epithelium.BMAL1 controls TNF and P21 during a pathologic state. TNF cytokine signaling increases epithelial proliferation in epithelial precursors to replace damaged epithelial cells. Rhythms in TNF production may arise from the epithelium but also are well known to be rhythmically produced by the immune system (see discussion). In epithelial cells, P21 response is under clock control downstream of TNF to regulate diurnal rhythms in cell production.