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.

Details

Title
Neonatally imprinted stromal cell subsets induce tolerogenic dendritic cells in mesenteric lymph nodes
Author
Pezoldt, Joern 1   VIAFID ORCID Logo  ; Pasztoi, Maria 1 ; Zou, Mangge 1 ; Wiechers, Carolin 1 ; Beckstette, Michael 1 ; Thierry, Guilhem R 2 ; Vafadarnejad, Ehsan 3 ; Floess, Stefan 1 ; Arampatzi, Panagiota 4   VIAFID ORCID Logo  ; Buettner, Manuela 5 ; Schweer, Janina 6 ; Fleissner, Diana 1 ; Vital, Marius 7 ; Pieper, Dietmar H 7 ; Basic, Marijana 8 ; Dersch, Petra 6 ; Strowig, Till 9   VIAFID ORCID Logo  ; Hornef, Mathias 10 ; Bleich, André 8   VIAFID ORCID Logo  ; Bode, Ulrike 11 ; Pabst, Oliver 12 ; Bajénoff, Marc 2 ; Antoine-Emmanuel Saliba 3   VIAFID ORCID Logo  ; Huehn, Jochen 1   VIAFID ORCID Logo 

 Department Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany 
 CNRS, INSERM, CIML, Aix Marseille University, Marseille, France 
 Helmholtz Institute for RNA-based Infection Research, Wuerzburg, Germany 
 Core Unit Systems Medicine, University of Wuerzburg, Wuerzburg, Germany 
 Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany; Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany 
 Department Molecular Infection Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany 
 Research Group Microbial Interactions and Processes, Helmholtz Centre for Infection Research, Braunschweig, Germany 
 Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany 
 Research Group Microbial Immune Regulation, Helmholtz Centre for Infection Research, Braunschweig, Germany 
10  Institute of Medical Microbiology, RWTH Aachen, Aachen, Germany 
11  Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany 
12  Institute of Molecular Medicine, RWTH Aachen, Aachen, Germany 
Pages
1-14
Publication year
2018
Publication date
Sep 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2112161568
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.