TβRIII is induced by TCR signaling and downregulated in FoxP3+ regulatory T cells

• Published in: Biochemical and biophysical research communications Vol. 494; no. 1-2; pp. 82 - 87
• Main Authors: Ortega-Francisco, Sandra, de la Fuente-Granada, Marisol, Alvarez Salazar, Evelyn K., Bolaños-Castro, Lizbeth Airais, Fonseca-Camarillo, Gabriela, Olguin-Alor, Roxana, Alemán-Muench, Germán R., López-Casillas, Fernando, Raman, Chander, García-Zepeda, Eduardo A., Soldevila, Gloria
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09-12-2017
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; APOPTOSIS; CELL DIFFERENTIATION; Down-Regulation; Forkhead Transcription Factors - metabolism; FoxP3; Humans; Immunologic Memory; IN VITRO; In Vitro Techniques; LIGANDS; Lymphocyte Activation; LYMPHOCYTES; Mice; Mice, Inbred C57BL; Mice, Transgenic; Proteoglycans - antagonists & inhibitors; Proteoglycans - genetics; Proteoglycans - metabolism; RECEPTORS; Receptors, Antigen, T-Cell - metabolism; Receptors, Transforming Growth Factor beta - antagonists & inhibitors; Receptors, Transforming Growth Factor beta - genetics; Receptors, Transforming Growth Factor beta - metabolism; Signal Transduction; SKELETON; STIMULATION; T lymphocyte; T-Lymphocytes, Regulatory - classification; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; TCR signaling; TGFβ; THYMOCYTES; TOLERANCE; TβRIII; Up-Regulation; TGFβ; TCR signaling; T lymphocyte; FoxP3; TβRIII
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.10.081

TGF-β type III receptor (TβRIII) is a co-receptor for TGFβ family members required for high-affinity binding of these ligands to their receptors, potentiating their cellular functions. TGF-βs, Bone Morphogenetic Proteins (BMP2/4) and Inhibins/Activins regulate different checkpoints during T cell differentiation. We have previously reported that TβRIII 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 TβRIII 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. TβRIII was upregulated after TCR stimulation, in parallel to other early activation markers. In contrast, natural and induced Tregs downregulated TβRIII in association with FoxP3 upregulation. Finally, anti-TβRIII blocking experiments demonstrated that TβRIII promotes TGFβ-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.
•TβRIII is expressed in murine and human T lymphocytes but not on B cells.•TβRIII is preferentially expressed in naïve and central memory T cells, but it is very lowly expressed on regulatory T cells.•TβRIII is upregulated by TCR signaling, following similar kinetics to other early activation markers.•TβRIII is downregulated during iTreg induction in association with FoxP3 upregulation.