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The mechanistic target of Rapamycin (mTOR) is essential for multiple cellular processes. The unique roles of mTOR complex 1 (mTORC1) or mTOR2 in regulating immune functions are emerging. NK cells are the major lymphocyte subset of innate immunity, and their development and effector functions require metabolic reprogramming. Recent studies demonstrate that in NK cells, conditionally disrupting the formation of mTORC1 or mTOR complex 2 (mTORC2) alters their development significantly. Transcriptomic profiling of NK cells at the single-cell level demonstrates that mTORC1 was critical for the early developmental progression, while mTORC2 regulated the terminal maturation. In this review, we summarize the essential roles of mTOR complexes in NK development and functions.
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http://dx.doi.org/10.3389/fcell.2020.566090 | DOI Listing |
Int J Biol Macromol
September 2025
Shaanxi Key Laboratory of Natural Products and Chemical Biology, College of Chemistry and Pharmacy, Northwest A&F University, Xianyang, China. Electronic address:
Pancreatic adenocarcinoma (PAAD) lacks effective therapies due to complex macromolecular signaling networks. Here, we identified the natural compound Trienomycin A (TA) as a potent binder and degrader of the key signaling adaptor protein Insulin Receptor Substrate 1 (IRS1), disrupting its macromolecular assembly in insulin-like growth pathways. Through integrated biochemical, cellular, and in vivo analyses, we demonstrated that TA directly bound the phosphotyrosine-binding (PTB) domain of IRS1, inducing proteasomal degradation of this critical macromolecular hub mediated by the E3 ubiquitin ligase FBXW8.
View Article and Find Full Text PDFFish Shellfish Immunol
September 2025
College of Marine Sciences, State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Life Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, China; Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and
The closely related cytokines Interleukin-4 (IL-4) and IL-13 regulate the Th2 immune response by interacting with their specific receptor complexes. MicroRNAs (miRNAs) modulate various biological pathways through mechanisms that either repress mRNA translation or promote messenger RNA degradation. The miRNA miR-126b is implicated in fish embryonic development.
View Article and Find Full Text PDFJ Neuroimmunol
September 2025
Laboratory of Physiology Pharmacology and Psychopathology, Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Chapecó, SC, Brazil. Electronic address:
The mammalian target of rapamycin (mTOR) has a role in immune regulation and neuroplasticity within the brain, influencing various neurological and psychiatric disorders, including bipolar disorder. mTOR signaling, via two complexes, mTORC1 and mTORC2, modulates immune responses by regulating microglial activation, cytokine production, and T-cell function. Dysregulation of these pathways leads to neuroinflammation, a hallmark of several neurological conditions.
View Article and Find Full Text PDFJ Clin Invest
September 2025
Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, United States of America.
B-lymphocytes play major adaptive immune roles, producing antibody and driving T-cell responses. However, how immunometabolism networks support B-cell activation and differentiation in response to distinct receptor stimuli remains incompletely understood. To gain insights, we systematically investigated acute primary human B-cell transcriptional, translational and metabolomic responses to B-cell receptor (BCR), Toll-like receptor 9 (TLR9), CD40-ligand (CD40L), interleukin-4 (IL4) or combinations thereof.
View Article and Find Full Text PDFG Ital Nefrol
August 2025
UO Nefrologia e Dialisi, Ospedale di Cassino, Italia.
SGLT-2 inhibitors are a relatively new class of antidiabetic drugs. They activate a transcriptional response similar to calorie restriction characterized by the up-regulation of sensors involved in nutrient deprivation, such as SIRT1 and AMPK, and the down-regulation of mTOR, a molecule involved in nutritional excess signaling. The purpose of this review is to illustrate the main pathways of nutrient deprivation: a complex mechanistic framework partly responsible for the cardio-renal benefits that makes these drugs unique.
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