Piceatannol inhibits effector T cell functions by suppressing TcR signaling

2015 ◽  
Vol 25 (2) ◽  
pp. 285-292 ◽  
Author(s):  
Do-Hyun Kim ◽  
Yong-Gab Lee ◽  
Hong-Jai Park ◽  
Jung-Ah Lee ◽  
Hyun Jung Kim ◽  
...  
2006 ◽  
Vol 177 (10) ◽  
pp. 6642-6649 ◽  
Author(s):  
Gopal Murugaiyan ◽  
Reena Agrawal ◽  
Gyan C. Mishra ◽  
Debashis Mitra ◽  
Bhaskar Saha

2015 ◽  
Vol 6 ◽  
Author(s):  
Vedran Brezar ◽  
Wen Juan Tu ◽  
Nabila Seddiki

2019 ◽  
Vol 2 (1) ◽  
pp. e201800282 ◽  
Author(s):  
Takayuki Imanishi ◽  
Midori Unno ◽  
Wakana Kobayashi ◽  
Natsumi Yoneda ◽  
Satoshi Matsuda ◽  
...  

Stimulator of interferon genes (STING) plays a key role in detecting cytosolic DNA and induces type I interferon (IFN-I) responses for host defense against pathogens. Although T cells highly express STING, its physiological role remains unknown. Here, we show that costimulation of T cells with the STING ligand cGAMP and TCR leads to IFN-I production and strongly inhibits T-cell growth. TCR-mediated mTORC1 activation and sustained activation of IRF3 are required for cGAMP-induced IFN-I production, and the mTORC1 activity is partially counteracted by cGAMP, thereby blocking proliferation. This mTORC1 inhibition in response to costimulation depends on IRF3 and IRF7. Effector T cells produce much higher IFN-I levels than innate cells in response to cGAMP. Finally, we demonstrated that STING stimulation in T cells is effective in inducing antitumor responses in vivo. Our studies demonstrate that the outputs of STING and TCR signaling pathways are mutually regulated through mTORC1 to modulate T-cell functions.


2011 ◽  
Vol 208 (12) ◽  
pp. 2545-2560 ◽  
Author(s):  
Hye-Ran Kim ◽  
Byeong-Hun Jeon ◽  
Hyun-Su Lee ◽  
Sin-Hyeog Im ◽  
Masatake Araki ◽  
...  

Immunoglobulin superfamily member 4 (IGSF4) is a known ligand of CRTAM, a receptor expressed in activated NKT and CD8+ T cells, but its function in T cell immunity has not been elucidated. In this study, we show that IGSF4 directly interacts with the T cell receptor (TCR) ζ-chain and enhances TCR signaling by enhancing ζ-chain phosphorylation. Ectopic overexpression of IGSF4 enhances TCR-mediated T cell activation. In contrast, IGSF4 knockdown shows a dramatic decrease in markers associated with T cell activation compared with those in control small interfering RNA. The transmembrane domain is essential for TCR ζ-chain association and clustering to the immunological synapse, and the ectodomain is associated with T cell interaction with antigen-presenting cells (APCs). IGSF4-deficient mice have impaired TCR-mediated thymocyte selection and maturation. Furthermore, these mice reveal attenuated effector T cell functions accompanied by defective TCR signaling. Collectively, the results indicate that IGSF4 plays a central role in T cell functioning by dual independent mechanisms, control of TCR signaling and control of T cell–APC interaction.


2019 ◽  
Vol 20 (14) ◽  
pp. 3500 ◽  
Author(s):  
Bommhardt ◽  
Schraven ◽  
Simeoni

In recent years, the lymphocyte-specific protein tyrosine kinase (Lck) has emerged as one of the key molecules regulating T-cell functions. Studies using Lck knock-out mice or Lck-deficient T-cell lines have shown that Lck regulates the initiation of TCR signaling, T-cell development, and T-cell homeostasis. Because of the crucial role of Lck in T-cell responses, strategies have been employed to redirect Lck activity to improve the efficacy of chimeric antigen receptors (CARs) and to potentiate T-cell responses in cancer immunotherapy. In addition to the well-studied role of Lck in T cells, evidence has been accumulated suggesting that Lck is also expressed in the brain and in tumor cells, where it actively takes part in signaling processes regulating cellular functions like proliferation, survival and memory. Therefore, Lck has emerged as a novel druggable target molecule for the treatment of cancer and neuronal diseases. In this review, we will focus on these new functions of Lck.


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