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- W2912147306 abstract "Lymph nodes (LNs) work as filtering organs, constantly sampling peripheral cues. This is facilitated by the conduit network, a parenchymal tubular-like structure formed of bundles of aligned extracellular matrix (ECM) fibrils ensheathed by fibroblastic reticular cells (FRCs). LNs undergo 5-fold expansion with every adaptive immune response and yet these ECM-rich structures are not permanently damaged. Whether conduit integrity and filtering functions are affected during cycles of LN expansion and resolution is not known. Here we show that the conduit structure is disrupted during acute LN expansion but FRC-FRC contacts remain intact. In homeostasis, polarised FRCs adhere to the underlying substrate to deposit ECM ba-solaterally. ECM production by FRCs is regulated by the C-type lectin CLEC-2, expressed by dendritic cells (DCs), at transcriptional and secretory levels. Inflamed LNs maintain conduit size-exclusion, but flow becomes leaky, which allows soluble antigens to reach more antigen-presenting cells. We show how dynamic communication between peripheral tissues and LNs changes during immune responses, and describe a mechanism that enables LNs to prevent inflammation-induced fibrosis. Highlights FRCs use polarized microtubule networks to guide matrix deposition CLEC-2/PDPN controls matrix production at transcriptional and post-transcriptional levels FRCs halt matrix production and decouple from conduits during acute LN expansion Conduits leak soluble antigen during acute LN expansion" @default.
- W2912147306 created "2019-02-21" @default.
- W2912147306 creator A5009703904 @default.
- W2912147306 creator A5011301544 @default.
- W2912147306 creator A5032930336 @default.
- W2912147306 creator A5036989588 @default.
- W2912147306 creator A5039520501 @default.
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- W2912147306 creator A5070121746 @default.
- W2912147306 creator A5074105722 @default.
- W2912147306 creator A5074887181 @default.
- W2912147306 creator A5077928677 @default.
- W2912147306 creator A5079825073 @default.
- W2912147306 creator A5091754913 @default.
- W2912147306 date "2019-01-23" @default.
- W2912147306 modified "2023-10-17" @default.
- W2912147306 title "Conduit integrity is compromised during acute lymph node expansion" @default.
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