Researchers from Wenzhou Medical College and Duke University confirmed that mTORC1 is a necessary condition for the development of constant natural killer cells (iNKT) and the function of effectors. The research results were published in the Proceedings of the American Academy of Sciences (PNAS).
Professor Jimin Gao of Wenzhou Medical College and Dr. Xiao-Ping Zhong of Duke University are co-corresponding authors of this paper. Professor Gao Jimin is mainly engaged in the immunological diagnosis and treatment of major diseases such as biotechnology, immunology, and tumor. Published more than 40 SCI research papers.
Natural killer T cells (NKT) are a type of lymphocytes with NK receptors and T cell receptors and showing both NK cell and T cell properties. They are one of the members of the innate immune system, and its main feature is T cell receptors ( TCR) The constancy of gene expression. Because its phenotypic function is different from immune cells such as T cells, B cells and NK cells, NKT cells can recognize the specific glycolipid molecules presented by CD1d and secrete a large amount of cytokines quickly. NKT cells can both enhance the immune response and suppress the immune response, thereby playing an important role in anti-infection, anti-tumor, suppression of autoimmune diseases and transplant tolerance.
iNKT cells are a unique subset of T lymphocytes and classic NKT cells, expressing both T cell surface markers, NK cell surface markers CD161 (NK1.1) and NK cell receptor P1C. However, at present, little is known about the developmental and functional regulatory mechanisms of iNKT cells.
Mammalian target of rapamycin (mTOR) is a Ser / Thr kinase present in mammalian cells. In mammals, mTOR can combine with other different proteins to form two complexes, mTORC1 and mTORC2. mTOR can regulate cell growth, proliferation, metabolism and survival by converging and integrating the stimulation signals from nutrition, growth factors, energy and environmental stress on cells. In recent years, a large number of studies have shown that mTOR is closely related to a series of important pathophysiological processes such as human inflammation, injury, hyperplasia, tissue repair, fibrosis, and tumor development.
In this article, the researchers confirmed that eliminating mTORC1 signaling by conditionally deleting Raptor can cause severe developmental defects in early iNKT cells, leading to a sharp reduction in the number of thymus and peripheral iNKT cells. In addition, the researchers confirmed in vivo and in vitro that Raptor deletion can reduce iNKT cell proliferation and cytokine production caused by α-galactosylceramide stimulation. In an iNKT cell-mediated hepatitis model, Raptor deletion suppressed liver inflammation.
As we all know, the transcription factor PLZF is not only important for iNKT cell development and effector programs, but also affects many other development programs. The researchers confirmed that mTORC1 is a key regulator of PLZF and controls the localization of PLZF to specific nuclear compartments. Absence of Raptor and rapamycin treatment can lead to abnormal localization and functional impairment of PLZF cells.
These results confirm that mTORC1 plays an essential role in guiding iNKT cell lineage development and effector function.
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