Format

Send to

Choose Destination
Nat Commun. 2018 Sep 25;9(1):3903. doi: 10.1038/s41467-018-06423-7.

Neonatally imprinted stromal cell subsets induce tolerogenic dendritic cells in mesenteric lymph nodes.

Author information

1
Department Experimental Immunology, Helmholtz Centre for Infection Research, 38124, Braunschweig, Germany.
2
CNRS, INSERM, CIML, Aix Marseille University, 13284, Marseille, France.
3
Helmholtz Institute for RNA-based Infection Research, 97080, Wuerzburg, Germany.
4
Core Unit Systems Medicine, University of Wuerzburg, 97080, Wuerzburg, Germany.
5
Institute of Functional and Applied Anatomy, Hannover Medical School, 30625, Hannover, Germany.
6
Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, 30625, Hannover, Germany.
7
Department Molecular Infection Biology, Helmholtz Centre for Infection Research, 38124, Braunschweig, Germany.
8
Research Group Microbial Interactions and Processes, Helmholtz Centre for Infection Research, 38124, Braunschweig, Germany.
9
Research Group Microbial Immune Regulation, Helmholtz Centre for Infection Research, 38124, Braunschweig, Germany.
10
Institute of Medical Microbiology, RWTH Aachen, 52074, Aachen, Germany.
11
Institute of Molecular Medicine, RWTH Aachen, 52074, Aachen, Germany.
12
Department Experimental Immunology, Helmholtz Centre for Infection Research, 38124, Braunschweig, Germany. Jochen.Huehn@helmholtz-hzi.de.

Abstract

Gut-draining mesenteric lymph nodes (mLNs) are important for inducing peripheral tolerance towards food and commensal antigens by providing an optimal microenvironment for de novo generation of Foxp3+ regulatory T cells (Tregs). We previously identified microbiota-imprinted mLN stromal cells as a critical component in tolerance induction. Here we show that this imprinting process already takes place in the neonatal phase, and renders the mLN stromal cell compartment resistant to inflammatory perturbations later in life. LN transplantation and single-cell RNA-seq uncover stably imprinted expression signatures in mLN fibroblastic stromal cells. Subsetting common stromal cells across gut-draining mLNs and skin-draining LNs further refine their location-specific immunomodulatory functions, such as subset-specific expression of Aldh1a2/3. Finally, we demonstrate that mLN stromal cells shape resident dendritic cells to attain high Treg-inducing capacity in a Bmp2-dependent manner. Thus, crosstalk between mLN stromal and resident dendritic cells provides a robust regulatory mechanism for the maintenance of intestinal tolerance.

PMID:
30254319
PMCID:
PMC6156403
DOI:
10.1038/s41467-018-06423-7
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center