TLR9 signaling in fibroblastic reticular cells regulates peritoneal immunity

Li Xu, Yiming Li, Chenxuan Yang, Patricia Loughran, Hong Liao, Rosemary Hoffman, Timothy R. Billiar, Meihong Deng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Fibroblastic reticular cells (FRCs), a subpopulation of stromal cells in lymphoid organs and fat-associated lymphoid clusters (FALCs) in adipose tissue, play immune-regulatory roles in the host response to infection and may be useful as a form of cell therapy in sepsis. Here, we found an unexpected major role of TLR9 in controlling peritoneal immune cell recruitment and FALC formation at baseline and after sepsis induced by cecal ligation and puncture (CLP). TLR9 regulated peritoneal immunity via suppression of chemokine production by FRCs. Adoptive transfer of TLR9-deficient FRCs more effectively decreased mortality, bacterial load, and systemic inflammation after CLP than WT FRCs. Importantly, we found that activation of TLR9 signaling suppressed chemokine production by human adipose tissue-derived FRCs. Together, our results indicate that TLR9 plays critical roles in regulating peritoneal immunity via suppression of chemokine production by FRCs. These data form a knowledge basis upon which to design new therapeutic strategies to improve the therapeutic efficacy of FRC-based treatments for sepsis and immune dysregulation diseases.

Original languageEnglish
Pages (from-to)3657-3669
Number of pages13
JournalJournal of Clinical Investigation
Volume129
Issue number9
DOIs
StatePublished - 3 Sep 2019
Externally publishedYes

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