Conduit Integrity is Compromised During Acute Lymph Node Expansion
| Autor: | Ian J. White, Janos Kriston-Vizi, Harry Horsnell, Agnesska C. Benjamin, Sophie E. Acton, Christopher J. Tape, Lukas Krasny, Tanya Singh, Víctor G. Martínez, Jemima J. Burden, Valeriya Pankova, Simone Dertschnig, Paul H. Huang |
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| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Chemistry Matrix (biology) respiratory system medicine.disease Acquired immune system Cell biology Extracellular matrix 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Immune system Electrical conduit Fibrosis Reticular cell 030220 oncology & carcinogenesis medicine Lymph PDPN Lymph node 030304 developmental biology |
| Zdroj: | SSRN Electronic Journal. |
| ISSN: | 1556-5068 |
| Popis: | 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.HighlightsFRCs use polarized microtubule networks to guide matrix depositionCLEC-2/PDPN controls matrix production at transcriptional and post-transcriptional levelsFRCs halt matrix production and decouple from conduits during acute LN expansionConduits leak soluble antigen during acute LN expansion |
| Databáze: | OpenAIRE |
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