Human BH3-only protein, Noxa, is a major contributor to proliferative metabolism and apoptosis in the CD8 +T cell immune response
نویسندگان
چکیده
Abstract Human Noxa, the smallest BH3-only Bcl-2 protein, was originally identified as pro-apoptotic, but has since also been shown to promote cell growth in both malignant and activated normal T cells by facilitating proliferative metabolism (Lowman et al., 2010, Mol Cell, 40, 823–33; Hanse 2017, Oncogene, 36, 3915–3924). To investigate contribution of Noxa immune response, we tracked its expression primary human CD8 +T an vitro anti-CD3/CD28 co-stimulation model. is undetectable naïve induced upon remains highly expressed during differentiation phase through onset apoptosis. The viable that remain following apoptosis at end response are ‘memory-like’, determined flow cytometry, harboring large mitochondria with robust spare respiratory capacity. These no longer express rapidly upregulate it re-stimulation. We observe protein cells, stimulation, directly dependent on glutamine unaffected glutaminase inhibitors, while entry carbons into TCA cycle, turn, requires Noxa. NoxaKO moreover, show reduced dependence significantly higher viability response. expressing deficient BH3 domain point mutant similarly presented extended effector phase. fundamental contributions activation-associated metabolic reprogramming a prototypic makes this attractive tool manipulate expansion, function, longevity for immunotherapy. R21 AI148876
منابع مشابه
Ultraviolet radiation triggers apoptosis of fibroblasts and skin keratinocytes mainly via the BH3-only protein Noxa
To identify the mechanisms of ultraviolet radiation (UVR)-induced cell death, for which the tumor suppressor p53 is essential, we have analyzed mouse embryonic fibroblasts (MEFs) and keratinocytes in mouse skin that have specific apoptotic pathways blocked genetically. Blocking the death receptor pathway provided no protection to MEFs, whereas UVR-induced apoptosis was potently inhibited by Bcl...
متن کاملHyperforin induces apoptosis of chronic lymphocytic leukemia cells through upregulation of the BH3-only protein Noxa.
We previously reported that hyperforin, a phloroglucinol purified from Hypericum perforatum, induces the mitochondrial pathway of caspase-dependent apoptosis in chronic lymphocytic leukemia (CLL) cells ex vivo, and that this effect is associated with upregulation of Noxa, a BH3-only protein of the Bcl-2 family. Here, we investigated the role of th...
متن کاملRegulation of the BH3-only protein NOXA in mantle cell lymphoma: relevance for novel treatment concepts
متن کامل
the fusion protein of ctp-hbcag18-27-tapasin mediates the apoptosis of cd8+t cells and cd8+ t cell response in hla-a2 transgenic mice
conclusions in conclusion, ctp-hbcag18-27-tapasin could reduce apoptosis of cd8+ t cells, increase the percentages of ifn-γ+ cd8α+ t cells, and elicit cell-mediated immunity in hla-a2 transgenic mice; these processes were associated with activation of the pi3k/akt signaling pathway. results the results showed that ctp-hbcag18-27-tapasin significantly increased the percentages of ifn-γ+ cd8α+ t ...
متن کاملIrradiated β-glucan enhances immune response to bacterial infection through CD4 and CD8 T-lymphocytes
Background: &beta-glucans are glucose polymers with a variety of stimulatory effects on the immune system. The objective of this study was to evaluate the immune-enhancing activities of low molecular weight gamma irradiated &beta-glucan (I&beta-g) extracted from Pleurotus ostreatus in response to Pseudomonas aeruginosa infection in rats. Materials and Methods: &beta-glucan (&beta-g) powder was ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.226.08