Thymic medullar conduits-associated podoplanin promotes natural regulatory T cells Journal Article


Author(s): Fuertbauer, Elke; Zaujec, Jan; Uhrin, Pavel; Raab, Ingrid; Weber, Michele; Schachner, Helga; Bauer, Miroslav; Schütz, Gerhard J; Binder, Bernd R; Sixt, Michael; Kerjaschki, Dontscho; Stockinger, Hannes
Article Title: Thymic medullar conduits-associated podoplanin promotes natural regulatory T cells
Affiliation IST Austria
Abstract: Podoplanin, a mucin-like plasma membrane protein, is expressed by lymphatic endothelial cells and responsible for separation of blood and lymphatic circulation through activation of platelets. Here we show that podoplanin is also expressed by thymic fibroblastic reticular cells (tFRC), a novel thymic medulla stroma cell type associated with thymic conduits, and involved in development of natural regulatory T cells (nTreg). Young mice deficient in podoplanin lack nTreg owing to retardation of CD4+CD25+ thymocytes in the cortex and missing differentiation of Foxp3+ thymocytes in the medulla. This might be due to CCL21 that delocalizes upon deletion of the CCL21-binding podoplanin from medullar tFRC to cortex areas. The animals do not remain devoid of nTreg but generate them delayed within the first month resulting in Th2-biased hypergammaglobulinemia but not in the death-causing autoimmune phenotype of Foxp3-deficient Scurfy mice.
Keywords: Fibroblastic reticular cells; natural regulatory T cells; thymopoiesis
Journal Title: Immunology Letters
Volume: 154
Issue 1-2
ISSN: 0165-2478
Publisher: Elsevier  
Date Published: 2013-07-01
Start Page: 31
End Page: 41
Sponsor: GEN-AU Program of the Austrian Federal Ministry of Education, Science and Culture; the EU-FP6 Framework Program “Lymphangiogenenomics” (LSHG-CT-2004-503573)
DOI: 10.1016/j.imlet.2013.07.007
Notes: We are grateful to Nicole Boucheron and Claudia Reichel for technical support.
Open access: no