Thymic medullar conduits-associated podoplanin promotes natural regulatory T cells

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• 作者：Elke Fuertbauer ; Jan Zaujec ; Pavel Uhrin ; Ingrid Raab ; Michele Weber ; Helga Schachner ; Miroslav Bauer ; Gerhard J. Sch¨¹tz ; Bernd R. Binder ; Michael Sixt ; Dontscho Kerjaschki ; Hannes Stockinger
• 关键词：Ab ; antibody ; alum ; aluminum hydroxide ; FRC ; fibroblastic reticular cell ; mAb ; monoclonal antibody ; nTreg ; natural regulatory T cell ; tFRC ; thymic fibroblastic reticular cells
• 刊名：Immunology Letters
• 出版年：2013
• 出版时间：July-August, 2013
• 年：2013
• 卷：154
• 期：1-2
• 页码：31-41
• 全文大小：5611 K

文摘

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.