Lymph node fibroblast phenotypes and immune crosstalk regulated by podoplanin activity
File(s)
Published version
Author(s)
Makris, Spyridon
Hari-Gupta, Yukti
Cantoral-Rebordinos, Jesús A
Martinez, Victor G
Horsnell, Harry L
Type
Journal Article
Abstract
Lymph nodes are uniquely organized niches for immune interactions. Fibroblastic reticular cells (FRCs) facilitate immune cell communication and regulate immune function by producing growth factors, chemokines, and inflammatory cues. Stromal expression of the glycoprotein podoplanin (PDPN) is required for lymph node development, but the requirement for PDPN signaling in FRCs in adult lymph nodes has not been directly tested. Using a conditional in vivo deletion model PDGFRαmGFPΔPDPN, single-cell RNA sequencing (scRNA-seq) reveals that PDPN deletion increases inflammatory signaling in lymph nodes and disrupts stromal-immune cell crosstalk in steady state and during adaptive immune responses. We confirm that PDPN/CLEC-2 signaling in FRCs switches transcriptional states and alters the expression of immune-related genes. We conclude that PDPN expression impacts the immunoregulatory properties of fibroblastic stroma in lymph nodes and is a key transcriptional regulator of fibroblast function in lymph nodes.
Date Issued
2025-07-22
Date Acceptance
2025-06-04
Citation
Cell Reports, 2025, 44 (7)
ISSN
2211-1247
Publisher
Elsevier BV
Journal / Book Title
Cell Reports
Volume
44
Issue
7
Copyright Statement
© 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
10.1016/j.celrep.2025.115908
Publication Status
Published
Article Number
115908
Date Publish Online
2025-06-27