Lymph node fibroblast phenotypes and immune crosstalk regulated by Podoplanin activity

Abstract

Lymph nodes are uniquely organised 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 PDGFRmGFP{Delta}PDPN, scRNA-seq revealed that PDPN deletion increased inflammatory signalling in lymph nodes and disrupted stromal-immune cells crosstalk in steady state and during adaptive immune responses. We confirmed that PDPN/CLEC-2 signaling in FRCs switches transcriptional states and alters expression of immune related genes. We conclude that Podoplanin expression impacts the immunoregulatory properties of fibroblastic stroma in lymph nodes and is a key transcriptional regulator of fibroblast function in lymph nodes. Summary: Podoplanin expression regulates the immunoregulatory properties of fibroblastic stroma in lymph nodes