Tissue retention of dendritic cells drives age-associated protective tolerogenic lymphoid structures
- 1Genentech Inc.
Abstract
Ectopic lymphoid structures are typically associated with chronic tissue inflammation in autoimmunity and cancer, where they can amplify local immune responses. Similar structures arise spontaneously with age, yet their origin and function remain unclear. Here we identify tissue retention of mature migratory conventional dendritic cells (cDCs) as a driver of age-associated lymphoid organization. Mature cDCs accumulated within lymphoid structures in aged human and mouse tissues. We demonstrate that impaired cDC egress or pharmacological cDC expansion induced de novo structures in mice across multiple otherwise homeostatic organs without associated pathology. Strikingly, senescence-associated tissue cues, which promoted a distinct cDC maturation state, were required for lymphoid niche initiation. Unlike inflammatory structures described in disease, these cDC-driven structures preferentially accumulated tissue-adapted regulatory T cells and protected against inflammatory injury, revealing a previously unrecognized regulatory dimension of age-associated lymphoid organization.
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BibTeX
@misc{marin2026tissue,
title = {{Tissue retention of dendritic cells drives age-associated protective tolerogenic lymphoid structures}},
author = {I. Marin and M. B. Morales and B. Orcutt-Jahns and J. Preston and K. Marroquin and z. yang and Y. Zhu and J. Webster and C. Moussion},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.04.756474},
url = {https://www.biorxiv.org/content/10.64898/2026.10.04.756474v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Tissue retention of dendritic cells drives age-associated protective tolerogenic lymphoid structures
AU - I. Marin
AU - M. B. Morales
AU - B. Orcutt-Jahns
AU - J. Preston
AU - K. Marroquin
AU - z. yang
AU - Y. Zhu
AU - J. Webster
AU - C. Moussion
PY - 2026
DA - 2026/10/04
PB - bioRxiv
DO - 10.64898/2026.10.04.756474
UR - https://www.biorxiv.org/content/10.64898/2026.10.04.756474v1
AB - Ectopic lymphoid structures are typically associated with chronic tissue inflammation in autoimmunity and cancer, where they can amplify local immune responses. Similar structures arise spontaneously with age, yet their origin and function remain unclear. Here we identify tissue retention of mature migratory conventional dendritic cells (cDCs) as a driver of age-associated lymphoid organization. Mature cDCs accumulated within lymphoid structures in aged human and mouse tissues. We demonstrate that impaired cDC egress or pharmacological cDC expansion induced de novo structures in mice across multiple otherwise homeostatic organs without associated pathology. Strikingly, senescence-associated tissue cues, which promoted a distinct cDC maturation state, were required for lymphoid niche initiation. Unlike inflammatory structures described in disease, these cDC-driven structures preferentially accumulated tissue-adapted regulatory T cells and protected against inflammatory injury, revealing a previously unrecognized regulatory dimension of age-associated lymphoid organization.
ER -