Conduit Integrity is Compromised During Acute Lymph Node Expansion

Abstract

Lymph nodes (LNs) act as filters, constantly sampling peripheral cues. This is facilitated by the conduit network, a tubular structure of aligned extracellular matrix (ECM) fibrils ensheathed by fibroblastic reticular cells (FRCs). LNs undergo 3-5-fold expansion during each adaptive immune response but these ECM-rich structures are not permanently damaged. Whether conduit integrity and filtering function is affected during LN expansion is unknown. Here we show that conduits are disrupted during acute LN expansion but FRC-FRC contacts remain connected. We reveal that polarised FRCs deposit ECM basolaterally utilising LL5-β, and that ECM production is regulated at transcriptional and secretory levels by the C-type lectin CLEC-2, expressed by dendritic cells. Inflamed LNs maintain conduit size-exclusion, but flow becomes leaky, allowing soluble molecules increased access to antigen-presenting cells. We show how dynamic communication between peripheral tissues and LNs changes during immune responses, and describe a mechanism enabling LNs to prevent inflammation-induced fibrosis.

Keywords: Fibroblastic reticular network, Conduit, Extracellular matrix, Lymph node, Pleckstrin Homology Like Domain Family B Member 2 (LL5-b)