New genetic model separates DC's innate and adaptive functions

The other day I reviewed an article where the authors used novel genetic model that could selectively delete classical/conventional DCs (cDC). It appears that this novel model is gaining popularity among scientists who are using it to re-define the role of classical DCs within immune system. I would remind you that prior to this model, people have used CD11c based genetic modification to assess DCs function. However, CD11c is expressed by other cells as well that could have influenced prior results.

In this new study published in Journal of Experimental Medicine, the authors led by Michel Nussenzweig, showed that cDC-selective deletion of MHCII leads to microbiota-driven gut inflammation.

This new genetic model is based on modification of gene called Zbtb46 (zDC) that is expressed in classical/conventional DCs (cDC), but not in monocytes, macrophages, and other myeloid cells (fate-mapping study). 

To separate cDC's innate and adaptive functions, the authors crossed zDC^Cre with MHCII^fl/fl mice to generate zDC^ΔMHCII mice that lack MHCII selectively on cDCs. cDCs from zDC^ΔMHCII mice showed normal "innate" function,

and as expected cDCs from zDC^ΔMHCII mice did not activate CD4 T cells upon antigen challenge.

Interestingly, zDC^ΔMHCII mice did not show any gross abnormality, except gut inflammation that was gut flora depended.

Finally, the authors showed that germ-free zDC^ΔMHCII mice colonized with defined flora produced reduced levels of T_FH cells and IgA.

In summary, this study showed that "adaptive" function of cDCs is important to maintain healthy gut homeostasis by generating CD4 T_FH dependent gut flora specific IgA.

David Usharauli