Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 60,161 bioRxiv papers from 267,433 authors.
Conduit integrity is compromised during acute lymph node expansion
Victor G. Martinez,
Ian J White,
Agnesska C Benjamin,
Harry L Horsnell,
Jemima J Burden,
Paul H Huang,
Christopher J Tape,
Sophie E Acton
Posted 23 Jan 2019
bioRxiv DOI: 10.1101/527481
Posted 23 Jan 2019
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 basolaterally. 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.
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