title: Association of T-zone reticular networks and conduits with ectopic lymphoid tissues in mice and humans.
abstract: 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 TLT 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 dendritic cells associated with them. They expressed lymphotoxin (LT) β receptor (LTβR), 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 LTβR and on lymphoid tissue inducer cells expressing LTβR 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.
authors: Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors: Alexander
authors: A
authors: Link
authors: Debbie L
authors: DL
authors: Hardie
authors: Stéphanie
authors: S
authors: Favre
authors: Mirjam R
authors: MR
authors: Britschgi
authors: David H
authors: DH
authors: Adams
authors: Michael
authors: M
authors: Sixt
authors: Jason G
authors: JG
authors: Cyster
authors: Christopher D
authors: CD
authors: Buckley
authors: Sanjiv A
authors: SA
authors: Luther
mesh_terms: D000818:Animals; D054382:Chemokine CXCL13 / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007328:Insulin / Q000235:genetics; D008024:Ligands; D008198:Lymph Nodes / Q000378:metabolism; D008221:Lymphoid Tissue / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020799:Pancrelipase / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D017154:Stromal Cells / Q000166:cytology
chemical_list: C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D007328:Insulin; D008024:Ligands; D020799:Pancrelipase