Figure 2. “Two-hit model” of microbiota for the pathogenesis of colitis.

Once intestinal immune homeostasis breaks, the microbiota stimulates mucosal DCs to produce IL-6 via TLR ligation. IL-6 promotes spontaneous proliferation of naïve T cells, which are in T0 status. T0 cells, in response to microbial antigens in the lamina propria, proliferate and upon TCR stimulation differentiate into Th1 and Th17 cells under the influence of IL-12 and IL-6/TGF-β, respectively, which eventually leads to intestinal inflammation. Adapted from Feng et al J Exp Med, 207, 1321–1332 (2010)⁵⁰.