Hippo/Mst signalling couples metabolic state and immune function of CD8α+ dendritic cells.

Nature
Xingrong DuHongbo Chi

Abstract

Dendritic cells orchestrate the crosstalk between innate and adaptive immunity. CD8α+ dendritic cells present antigens to CD8+ T cells and elicit cytotoxic T cell responses to viruses, bacteria and tumours 1 . Although lineage-specific transcriptional regulators of CD8α+ dendritic cell development have been identified 2 , the molecular pathways that selectively orchestrate CD8α+ dendritic cell function remain elusive. Moreover, metabolic reprogramming is important for dendritic cell development and activation3,4, but metabolic dependence and regulation of dendritic cell subsets are largely uncharacterized. Here we use a data-driven systems biology algorithm (NetBID) to identify a role of the Hippo pathway kinases Mst1 and Mst2 (Mst1/2) in selectively programming CD8α+ dendritic cell function and metabolism. Our NetBID analysis reveals a marked enrichment of the activities of Hippo pathway kinases in CD8α+ dendritic cells relative to CD8α- dendritic cells. Dendritic cell-specific deletion of Mst1/2-but not Lats1 and Lats2 (Lats1/2) or Yap and Taz (Yap/Taz), which mediate canonical Hippo signalling-disrupts homeostasis and function of CD8+ T cells and anti-tumour immunity. Mst1/2-deficient CD8α+ dendritic cells are impaired in pr...Continue Reading

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Datasets Mentioned

BETA
GSE100772
PXD006875

Methods Mentioned

BETA
proteomics profiling
PCR
immunodepletion
density-gradient centrifugation
flow cytometry
protein assay
transfection

Software Mentioned

FlowJo
ARACNE
Elements
limma
NetBID
JUMP
house
Partek Genomics Suite
GraphPad
JUMP engine

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