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Biochem Biophys Res Commun ; 494(1-2): 82-87, 2017 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-29050936

RESUMO

TGF-ß type III receptor (TßRIII) is a co-receptor for TGFß family members required for high-affinity binding of these ligands to their receptors, potentiating their cellular functions. TGF-ßs, Bone Morphogenetic Proteins (BMP2/4) and Inhibins/Activins regulate different checkpoints during T cell differentiation. We have previously reported that TßRIII modulates T cell development by protecting developing thymocytes from apoptosis, however the role of this co-receptor in peripheral lymphocytes still remains elusive. Here we describe a detailed characterization of TßRIII expression in murine and human lymphocyte subpopulations demonstrating that this co-receptor is significantly expressed in T but not B lymphocytes and among them, preferentially expressed on naïve and central memory T cells. TßRIII was upregulated after TCR stimulation, in parallel to other early activation markers. In contrast, natural and induced Tregs downregulated TßRIII in association with FoxP3 upregulation. Finally, anti-TßRIII blocking experiments demonstrated that TßRIII promotes TGFß-dependent iTreg conversion in vitro, and suggest that this co-receptor may be involved in modulating peripheral T cell tolerance and could be considered as a potential target to boost T cell immune responses.


Assuntos
Proteoglicanas/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Linfócitos T Reguladores/imunologia , Animais , Regulação para Baixo , Fatores de Transcrição Forkhead/metabolismo , Humanos , Memória Imunológica , Técnicas In Vitro , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteoglicanas/antagonistas & inibidores , Proteoglicanas/genética , Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores , Receptores de Fatores de Crescimento Transformadores beta/genética , Transdução de Sinais , Linfócitos T Reguladores/classificação , Linfócitos T Reguladores/metabolismo , Regulação para Cima
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