Regulatory T (Treg) cells are crucial for the maintenance of autoimmunity homeostasis and are also important reason for the formation of tumor-suppressive microenvironments. It has been reported that Treg cells undergo an activation process similar to that of CD4 T cells and eventually differentiate into effector Treg cells, which can secrete inhibitory cytokines and exert immunosuppressive functions. TGF-β, IL-10 is a commonly studied immunosuppressive factor. In recent years, studies have found that Treg cells secrete a new type of inhibitory cytokine IL-35, which has been shown to have strong immunosuppressive capacity both in vivo and in vitro and can cause infectious immunity in infectious diseases and tumors Tolerance. However, due to the lack of suitable antibodies, it is still very difficult to detect IL-35-secreting cells. Known studies are based on the detection of the overall cellular level by RT-PCR and ELISA, but lack of ability to secrete IL-35 Cell deep and detailed understanding.
In order to further study the inhibitory function of Treg cells, a group of reporter gene mice (Ebi3-Dre-Thy1.1 mice) of IL-35 were constructed using a BAC transgenic technique by a research team led by Xuyu Zhou, Institute of Microbiology of Chinese Academy of Sciences. The expression of Thy 1.1 on the cell surface can be used to indicate the intracellular IL-35 secretion and the function of IL-35 secreting cells can be studied in vivo by injection of Thy 1.1 antibody. The reporter found that the IL-35 secreting cells in mice mainly derived from thymus-derived tTreg cells. Further analysis of the surface molecules and transcriptional profiling revealed that IL-35-Treg secreting IL-35 and IL-10-Treg secreting IL-10 are two groups of completely independent effector Treg subsets with different surface markers, tissue distribution and transcription factor dependence. The expression of CCR7 in IL-35-Treg cells tends to stay in the T cell area and plays an important role in the inhibition of tumor immunity. IL-35-Treg does not depend on the expression of the transcription factor Blimp1. IL-10-Treg cells secrete high levels of IL-10 and a variety of granzymes (Gzms), high expression of a variety of chemokine receptors (such as CCR5 and CCR4, etc.), tend to migrate to the peripheral immune suppression occurred; Unlike IL-35-Treg, IL-10-Treg cells are strictly dependent on the expression of the transcription factor Blimp1. This study demonstrates that IL-35-Treg and IL-10-Treg are functionally complementary and work together to maintain the body's immune tolerance.
In his research work, Xuyu Zhou 's team used the reporter gene mouse as a research tool to reveal the different effector Treg cell subsets (IL-35-Treg and IL-10-Treg) both phenotypically and functionally. The study will enrich the understanding of Treg immunosuppressive mechanisms or provide new therapeutic strategies for a variety of autoimmune diseases, infectious diseases and cancers.
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Xundong Wei, Jianhua Zhang, Qianchong Gu, Man Huang, Wei Zhang, Jie Guo, Xuyu Zhou, Reciprocal Expression of IL-35 and IL-10 Defines Two Distinct Effector Treg Subsets that Are Required for Maintenance of Immune Tolerance, Cell Reports, Volume 21, Issue 7, 14 November 2017, Pages 1853-1869, ISSN 2211-1247
