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The Notch signaling controls maintenance of memory CD4+ T cells

 

In the process of immune response, CD4+ T cell can differentiate into short-lived effector cell or long-lived memory cell, which is important for secondary immune responses. However, autoreactive memory CD4+ T cells could be harmful for the body. Recently, Maekawa et al. demonstrated Notch signaling is important for the survival of memory CD4+ T cells by regulating glucose uptake. The article was published on Nature Medicine.

 

Notch signaling pathway involves in control of differentiation and fate determination of multiple cell types. The inhibition of Notch signaling impaired the survival of memory CD4+ T cells. Also, the recombination signal binding protein for immunoglobulin κJ region (Rbpj) that binds to the intracellular domain of Notch signaling, is required for the maintenance of memory CD4+ T cells. In addition, the Notch-mediated maintenance of memory CD4+ T cells is independent from Stat5 and mTOR signaling, two pathways related to cell proliferation and survival. Furthermore, in the absent of Rbpj, memory CD4+ T cells showed a decrease of glucose uptake and a low expression level of Glut1, which were proved to be regulated by Notch signaling. Taken together, Notch signaling is critical in the regulation of memory CD4+ T cells survival, via mediating glucose uptake. Therefore, the control of Notch signaling and glucose metabolism might be two promising strategies for inhibition or enhancement the survival of memory CD4+ T cells

 

Reference:
Nat Med. 2014 Dec 15;10.1038/nm.3758.

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S2714 LY411575 LY411575 is a potent γ-secretase inhibitor with IC50 of 0.078 nM/0.082 nM (membrane/cell-based), also inhibits Notch cleavage with IC50 of 0.39 nM in APP or NΔE expressing HEK293 cells. LY411575 induces apoptosis.
S1039 Rapamycin (Sirolimus) Rapamycin (Sirolimus) is a specific mTOR inhibitor with IC50 of ~0.1 nM HEK293 cells.Rapamycin binds to FKBP12 and specifically acts as an allosteric inhibitor of mTORC1. Rapamycin is an autophagy activator and an immunosuppressant.

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STAT mTOR Gamma-secretase