PD-L1+ and XCR1+ dendritic cells are region-specific regulators of gut homeostasis.
Thais G MoreiraDavide ManganiLaura Michelle CoxJeffrey LeibowitzEduardo L C LoboMariana A OliveiraChristian D GauthierBrenda N NakagakiValerie WillocqAnya SongLydia GuoDavid C A LimaGopal MurugaiyanOleg ButovskyGalina GabrielyAna Carrizosa AndersonRafael M RezendeAna Maria C FariaHoward L WeinerPublished in: Nature communications (2021)
The intestinal mucosa constitutes an environment of closely regulated immune cells. Dendritic cells (DC) interact with the gut microbiome and antigens and are important in maintaining gut homeostasis. Here, we investigate DC transcriptome, phenotype and function in five anatomical locations of the gut lamina propria (LP) which constitute different antigenic environments. We show that DC from distinct gut LP compartments induce distinct T cell differentiation and cytokine secretion. We also find that PD-L1+ DC in the duodenal LP and XCR1+ DC in the colonic LP comprise distinct tolerogenic DC subsets that are crucial for gut homeostasis. Mice lacking PD-L1+ and XCR1+ DC have a proinflammatory gut milieu associated with an increase in Th1/Th17 cells and a decrease in Treg cells and have exacerbated disease in the models of 5-FU-induced mucositis and DSS-induced colitis. Our findings identify PD-L1+ and XCR1+ DC as region-specific physiologic regulators of intestinal homeostasis.
Keyphrases
- dendritic cells
- regulatory t cells
- immune response
- induced apoptosis
- transcription factor
- cell cycle arrest
- gene expression
- skeletal muscle
- type diabetes
- radiation therapy
- cell death
- single cell
- genome wide
- oxidative stress
- dna methylation
- rna seq
- diabetic rats
- endothelial cells
- adipose tissue
- endoplasmic reticulum stress
- metabolic syndrome
- radiation induced
- stress induced