MEDICINE AND HEALTH

The study of immune regulatory mechanisms provides new ideas for cancer treatment


On May 25, Science Advances published a research paper online by Professor Chen Fuxiang of the Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and Jun Yan, a professor at the University of Louisville. This paper reveals the immune metabolism regulation mechanism of special immune cells γδ T, which provides new clues for the basic research and directional differentiation mechanism of γδ T cell biology, and provides new ideas for immunotherapy for clinical diseases (such as cancer).

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Metabolic regulation mechanism of immune cell γδ T Courtesy of the interviewee

The immune system is composed of immune organs, immune cells and immune molecules, in which immune cells such as T cells play an important role, T cells can express T cell receptors (TCR) to recognize antigens and mediate immune responses, T cells are divided into αβT cells and γδ T cells according to the different structure of the TCR peptide chain, so in T lymphocytes, in addition to the common αβT cells, there is a special group of cells, for TTRγδ T cells. Although the number of gamma t cells is small, they are widely distributed in the body, especially in mucosal tissues, and play an important role in physiological or pathological processes.

According to the different cytokines secreting cytokines, γδ T cells can be divided into γδ T17 cells that secrete interleukin-17 and γ γδ T1 cells that secrete interferons.

“The study found differences in the main metabolic pathways between gamma T1 cells and γδ T17 cells, with gamma t1 cells relying mainly on glycolysis to provide energy, while γδ T17 cells rely on glutamine metabolism and tricarboxylic acid cycling.” Chen Fuxiang said, “Through small interference RNA technology and lentiviral transfection technology, we found that IDH2 has the role of key metabolic enzymes in the cytokine secretion function of γδ T cells, and the transcription factor c-Maf is also highly expressed in γδ T17 cells, and co-expressed with the core transcription factor RORγt that regulates interleukin-17.” ”

By further constructing conditioned knockout mice for experiments, the researchers revealed that transcription factor c-Maf can directly regulate the key metabolic enzyme IDH2 in γδ T17 cells to mediate the secretion of interleukin-17, further providing new clues to reveal the biology of γδ T cells and the mechanism of directed differentiation.

At the same time, the cooperative team focused on oral squamous cell carcinoma, a clinical feature of the nine hospitals, and used single-cell sequencing technology to analyze γδ T cells in oral squamous cell carcinoma, and found that a certain proportion of γδ T17 cells were present in oral squamous cell carcinoma tissues and these cells expressed high c-Maf, and these research results provided new ideas for the clinical immunotherapy of oral squamous cell carcinoma. (Source: China Science Daily, Zhang Shuanghu, Huang Xin)

Related paper information:https://doi.org/10.1126/sciadv.abm9120

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