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

Abstract

The NF-κB 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 naïve 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.

Keywords: Immune regulation; Lung inflammation; NF-κB pathway; Spleen; Th2.