Abstract
TGF-β type III receptor (TβRIII) is a coreceptor for TGFβ family members required for high-affinity binding of these ligands to their receptors, potentiating their cellular functions. TGF-β [1]–[3], bone morphogenetic proteins (BMP2/4) and inhibins regulate different checkpoints during T cell differentiation. Although TβRIII is expressed on hematopoietic cells, the role of this receptor in the immune system remains elusive. Here, we provide the first evidence that TβRIII is developmentally expressed during T cell ontogeny, and plays a crucial role in thymocyte differentiation. Blocking of endogenous TβRIII in fetal thymic organ cultures led to a delay in DN-DP transition. In addition, in vitro development of TβRIII−/− thymic lobes also showed a significant reduction in absolute thymocyte numbers, which correlated with increased thymocyte apoptosis, resembling the phenotype reported in Inhibin α −/− thymic lobes. These data suggest that Inhibins and TβRIII may function as a molecular pair regulating T cell development.
Highlights
T cell development requires the recognition of self-peptide MHC complexes by immature thymocytes, leading to the selection of a self-restricted and autotolerant T cell repertoire
In order to determine if TbRIII signaling might have a role in fetal thymocyte development, we analyzed the gene expression of the receptor in embryonic day 14 (E14), E15 and E16 fetal thymi and compared it to that in adult thymi
TbRIII Expression is Regulated during T Cell Ontogeny Since type I and type II TGFb receptors are differentially expressed in thymocyte subsets and their expression is associated with distinct thymocyte responsiveness to TGF-b superfamily ligands [4,5,33], we investigated whether TbRIII is differentially expressed on the cell surface of developing thymocytes
Summary
T cell development requires the recognition of self-peptide MHC complexes by immature thymocytes, leading to the selection of a self-restricted and autotolerant T cell repertoire. Given that downstream signaling of many TGF-b ligands are regulated by TbRIII to fine tune key cellular processes, here we investigated the expression of TbRIII in the thymus and its potential role in T cell differentiation.
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