Biology subjects

Horsnell, H. L.

Publications and source records attributed to Horsnell, H. L..

2 recordsLinked to original sources

bioRxiv2022

Podoplanin expression in fibroblasts determines lymph node architecture and adaptive immune function

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

immunology↗

bioRxiv2021

Mechanical Forces during Lymph Node Expansion Govern Fibroblastic Reticular Network Remodeling

Emergent physical properties of tissues are not readily understood by reductionist studies of their constituent cells. Here, we show molecular signals controlling cellular physical properties, collectively determining tissue mechanics of lymph nodes, an immunologically-relevant, adult mammalian tissue. Lymph nodes paradoxically maintain robust tissue architecture in homeostasis yet are continually poised for extensive tissue expansion upon immune challenge. We find that following immune challenge, cytoskeletal mechanics of a cellular meshwork of fibroblasts determine tissue tension independently of extracellular matrix scaffolds. We determine that CLEC-2/podoplanin signalling regulates the cell surface mechanics of fibroblasts, permitting cell elongation and interdigitation through expedited access to plasma membrane reservoirs. Increased tissue tension through the stromal meshwork gates the initiation of fibroblast proliferation, restoring homeostatic cellular ratios and tissue structure through expansion.

biophysics↗