A noncanonical NF-kB - β-catenin signaling axis in dendritic cells instructs gut inflammation

Abstract Dendritic cells (DCs) balance intestinal homeostasis against inflammatory insults. In particular, the noncanonical NF-kB pathway, which activates RelB:p52 heterodimers, has been implicated in DC differentiation. However, if DC-intrinsic signaling modulates function inflamed gut remains unclear. Here we report that genetic ablation of DCs accumulated regulatory T lamina propria and associated lymph nodes, restraining inflammation colitogenic gut. Our mechanistic investigation revealed an impaired gene function, rather unexpectedly, augmented abundance active β-catenin via impairment destruction complex. turn, transcriptionally upregulated Raldh2, imparting a retinoic acid signature tolerogenic functions to NF-kB-deficient DCs. Indeed, mice possessing defects exhibited increased frequency +DCs resilience chemical induced experimental colitis. Taken together, chart novel crosstalk between pathway instructs National Institute Immunology Core funding BT/PR36631/BRB/10/1862/2020, Department Biotechnology (DBT).