The differential organogenesis and functionality of two liver-draining lymph nodes in mice.

The liver is an immunological organ. However, fundamental knowledge concerning liver-draining lymph nodes (LNs), which have been newly identified in mice as the portal and celiac LNs, is still lacking. Here, we revealed that the portal LN and celiac LN drain liver lymph through different lymphatic vessels. Although both the portal LN and celiac LN possess typical structures, they have different cell compositions. Interestingly, these two LNs form at different times during fetal development. Moreover, the organogenesis of the celiac LN, but not the portal LN, is controlled by the transcription factor NFIL3. Furthermore, the portal LN and celiac LN also perform different functions. The celiac LN is the predominant site of liver antiviral immune responses, whereas the portal LN functions in the in situ induction of dietary antigen-specific regulatory T cells. In conclusion, the portal LN and celiac LN are two independent liver-draining LNs with different organogenesis histories and separate functions in maintaining immune homeostasis in the liver.