Mind Bomb-1 in Dendritic Cells Is Specifically Required for Notch-mediated T Helper Type 2 Differentiation

In dendritic cell (DC)-CD4(+) T cell interaction, Notch signaling has been implicated in the CD4(+) T cell activation, proliferation, and subset differentiation. However, there has been a lot of debate on the exact role of Notch signaling. Here, we observed that expression of Mind bomb-1 (Mib1), a critical regulator of Notch ligands for the activation of Notch signaling, increases gradually as precursor cells differentiate into DCs in mice. To clarify the role of Mib1 in DC-CD4(+) T cell interactions, we generated Mib1-null bone marrow-derived DCs. These cells readily expressed Notch ligands but failed to initiate Notch activation in the adjacent cells. Nevertheless, Mib1-null DCs were able to prime the activation and proliferation of CD4(+) T cells, suggesting that Notch activation in CD4(+) T cells is not required for these processes. Intriguingly, stimulation of CD4(+) T cells with Mib1-null DCs resulted in dramatically diminished Th2 cell populations, while preserving Th1 cell populations, both in vitro and in vivo. Our results demonstrate that Mib1 in DCs is critical for the activation of Notch signaling in CD4(+) T cells, and Notch signaling reinforces Th2 differentiation, but is not required for the activation or proliferation of the CD4(+) T cells.