Details

Autor(en) / Beteiligte

• Pezoldt, Joern
• Pasztoi, Maria
• Zou, Mangge
• Wiechers, Carolin
• Beckstette, Michael
• Thierry, Guilhem R
• Vafadarnejad, Ehsan
• Floess, Stefan
• Arampatzi, Panagiota
• Buettner, Manuela
• Schweer, Janina
• Fleissner, Diana
• Vital, Marius
• Pieper, Dietmar H
• Basic, Marijana
• Dersch, Petra
• Strowig, Till
• Hornef, Mathias
• Bleich, André
• Bode, Ulrike
• Pabst, Oliver
• Bajénoff, Marc
• Saliba, Antoine-Emmanuel
• Huehn, Jochen

Titel

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

Ist Teil von

• Nature communications, 2018-09, Vol.9 (1), p.3903-14, Article 3903

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.