Association of T-Zone Reticular Networks and Conduits with Ectopic Lymphoid Tissues in Mice and Humans

A Link, Deborah Hardie, S Favre, MR Britschgi, David Adams, M Sixt, JG Cyster, Christopher Buckley, SA Luther

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Ectopic or tertiary lymphoid tissues (TLTs) are often induced at sites of chronic inflammation. They typically contain various hematopoietic cell types, high endothelial venules, and follicular dendritic cells; and are organized in lymph node-like structures. Although fibroblastic stromal cells may play a role in UT induction and persistence, they have remained poorly defined. Herein, we report that TLTs arising during inflammation in mice and humans in a variety of tissues (eg, pancreas, kidney, liver, and salivary gland) contain stromal cell networks consisting of podoplanin(+) T-zone fibroblastic reticular cells (TRCs), distinct from follicular dendritic cells. Similar to lymph nodes, TRCs were present throughout T-cell-rich areas and had dentritic cells associated with them. They expressed lymphotoxin (LT) beta receptor (LT beta R), produced CCL21, and formed a functional conduit system. In rat insulin promoter-CXCL13-transgenic pancreas, the maintenance of TRC networks and conduits was partially dependent on LT beta R and on lymphoid tissue inducer cells expressing LT beta R ligands. In conclusion, TRCs and conduits are hallmarks of secondary lymphoid organs and of well-developed TLTs, in both mice and humans, and are likely to act as important scaffold and organizer cells of the T-cell-rich zone. (Am J Pathol 2011, 178:1662-1675; DOI: 10.1016/j.ajpath.2010.12.039)
Original languageEnglish
Pages (from-to)1662-1675
Number of pages14
JournalThe American Journal of Pathology
Issue number4
Early online date22 Mar 2011
Publication statusPublished - 1 Apr 2011


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