title: Thymic medullar conduits-associated podoplanin promotes natural regulatory T cells.
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.
authors.affiliation: Molecular Immunology Unit, Institute for Hygiene and Applied Immunology, Centre for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Lazarettgasse 19, 1090 Vienna, Austria.
authors.forename: Elke
authors.initials: E
authors.lastname: Fuertbauer
authors.forename: Jan
authors.initials: J
authors.lastname: Zaujec
authors.forename: Pavel
authors.initials: P
authors.lastname: Uhrin
authors.forename: Ingrid
authors.initials: I
authors.lastname: Raab
authors.forename: Michele
authors.initials: M
authors.lastname: Weber
authors.forename: Helga
authors.initials: H
authors.lastname: Schachner
authors.forename: Miroslav
authors.initials: M
authors.lastname: Bauer
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Schütz
authors.forename: Bernd R
authors.initials: BR
authors.lastname: Binder
authors.forename: Michael
authors.initials: M
authors.lastname: Sixt
authors.forename: Dontscho
authors.initials: D
authors.lastname: Kerjaschki
authors.forename: Hannes
authors.initials: H
authors.lastname: Stockinger
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D054421:Chemokine CCL21 / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009077:Mucins / Q000378:metabolism; D020239:Receptor Cross-Talk; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D000098853:Podoplanin
chemical_list: D015704:CD4 Antigens; D054421:Chemokine CCL21; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D008562:Membrane Glycoproteins; D009077:Mucins; C498833:Foxp3 protein, mouse; C490441:Pdpn protein, mouse; D000098853:Podoplanin
keywords: Ab; FRC; Fibroblastic reticular cells; Natural regulatory T cells; Thymopoiesis; alum; aluminum hydroxide; antibody; fibroblastic reticular cell; mAb; monoclonal antibody; nTreg; natural regulatory T cell; tFRC; thymic fibroblastic reticular cells