# TLR ligand sensing by lymph node FRCs directs intranodal lymphocyte accumulation to promote immune responses

## TL;DR

Lymph node stromal cells use Toll-like receptors to sense infections and boost immune responses by attracting lymphocytes.

## Contribution

TLR signaling in lymph node fibroblastic reticular cells drives rapid lymphocyte accumulation and enhances immune responses.

## Key findings

- TLR ligand sensing by FRCs rapidly increases homeostatic chemokine expression.
- TLR signaling in FRCs is critical for lymphocyte accumulation and effective immune responses.
- Ablation of TLR signaling in FRCs reduces vaccine efficacy against tumors.

## Abstract

Immune protection depends on antigen-responsive lymphocytes finding their cognate antigen on competent antigen-presenting cells. To increase the likelihood of such an event happening, lymphocytes transiently accumulate in secondary lymphoid organs soon after infection. Here, we show that this phenomenon requires expression of Toll-like receptors (TLRs) on lymph node stromal cells. Direct sensing of pathogen-associated molecular patterns by TLR-expressing fibroblastic reticular cells (FRCs) rapidly induced homeostatic chemokine expression, mediating immediate lymphocyte accumulation into reactive lymph nodes. Ablation of this response, by means of Tlr4−/− lymph node transplantation or conditional Tlr4 gene deletion on PDGFRb+ cells, reduced the number of lymphocytes recruited into the immune response limiting vaccine efficacy against tumors. Taken together, these observations provide further evidence for a critical role of early FRC activation in driving effective immunity, placing these non-hematopoietic cells at the center of adaptive host protection.

•LPS exposure triggers rapid, CCR7-dependent intranodal lymphocyte accumulation•Lymph node FRCs respond to LPS exposure rapidly with increased CCL19/CCL21 production•FRC responses to LPS mediate intranodal lymphocyte accumulation•FRC responses to LPS power T cell responses quantitatively

LPS exposure triggers rapid, CCR7-dependent intranodal lymphocyte accumulation

Lymph node FRCs respond to LPS exposure rapidly with increased CCL19/CCL21 production

FRC responses to LPS mediate intranodal lymphocyte accumulation

FRC responses to LPS power T cell responses quantitatively

Biological sciences; Immunology