A new RelB-dependent CD117+CD172a+ murine DC subset preferentially induces Th2 differentiation and supports airway hyperresponses in vivo

The NF-B transcription factor subunit RelB is important for the full activation of conventional dendritic cells (cDCs) during T-cell-dependent immune responses. Although the number of splenic DCs is greatly reduced in RelB(null) mice, the cause and consequences of this deficiency are currently unknown. To circumvent the impact of the pleiotropic defects in RelB(null) mice we used a reporter model for RelB expression (RelB(Katushka) mice) and conditionally deleted RelB in DCs (RelB(CD11c-Cre) mice). Thereby, we can show here that RelB is essential for the differentiation of a CD117(+)CD172a(+) cDC subpopulation that highly expresses RelB. Surprisingly, these DCs depend on p50 for their development and are negatively regulated by a constitutive p52 activation in absence of p100. The absence of p52/p100 had no influence on the homeostasis of CD117(+)CD172a(+) cDCs. RelB-dependent CD117(+)CD172a(+) DCs strongly induce the production of the type 2 cytokines IL-4 and IL-13, as well as GM-CSF from naive Th cells. Consequently, mice lacking RelB in cDCs show an attenuated bronchial hyperresponsiveness with reduced eosinophil infiltration. Taken together, we have identified a new splenic RelB-dependent CD117(+)CD172a(+) cDC population that preferentially induces Th2 responses.