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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