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

Joern Pezoldt, Maria Pasztoi, Mangge Zou, Carolin Wiechers, Michael Beckstette, Guilhem R. Thierry, Ehsan Vafadarnejad, Stefan Floess, Panagiota Arampatzi, Manuela Buettner, Janina Schweer, Diana Fleissner, Marius Vital, Dietmar H. Pieper, Marijana Basic, Petra Dersch, Till Strowig, Mathias Hornef, André Bleich, Ulrike Bode, Oliver Pabst, Marc Bajénoff, Antoine-Emmanuel Saliba and Jochen Huehn ()
Additional contact information
Joern Pezoldt: Helmholtz Centre for Infection Research
Maria Pasztoi: Helmholtz Centre for Infection Research
Mangge Zou: Helmholtz Centre for Infection Research
Carolin Wiechers: Helmholtz Centre for Infection Research
Michael Beckstette: Helmholtz Centre for Infection Research
Guilhem R. Thierry: Aix Marseille University
Ehsan Vafadarnejad: Helmholtz Institute for RNA-based Infection Research
Stefan Floess: Helmholtz Centre for Infection Research
Panagiota Arampatzi: University of Wuerzburg
Manuela Buettner: Hannover Medical School
Janina Schweer: Helmholtz Centre for Infection Research
Diana Fleissner: Helmholtz Centre for Infection Research
Marius Vital: Helmholtz Centre for Infection Research
Dietmar H. Pieper: Helmholtz Centre for Infection Research
Marijana Basic: Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School
Petra Dersch: Helmholtz Centre for Infection Research
Till Strowig: Helmholtz Centre for Infection Research
Mathias Hornef: Institute of Medical Microbiology, RWTH Aachen
André Bleich: Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School
Ulrike Bode: Hannover Medical School
Oliver Pabst: Institute of Molecular Medicine, RWTH Aachen
Marc Bajénoff: Aix Marseille University
Antoine-Emmanuel Saliba: Helmholtz Institute for RNA-based Infection Research
Jochen Huehn: Helmholtz Centre for Infection Research

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06423-7

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DOI: 10.1038/s41467-018-06423-7

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