For the first time, the molecular mechanism of regulating the final maturity of iNKT cell differentiation is revealed.

On September 24th, the international academic journal Nature Communications published the latest research results of the Liu Xiaolong Research Group of the Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences, "The Regulation of the Terminal Maturation of the iNKT cells by the mediator sydd subunit 23", revealing for the first time the molecular mechanism of regulating the final maturity of iNKT cell differentiation.
iNKT cells are a specific group of T-cell subgroups that express specific T-cell receptors (TCR) and NK cell surface receptors (NK1.1).
iNKT cells, unlike classic T cells, can identify MHC-I molecular analogue CD1d molecules presented glycolipid antigens, after antigen stimulation, can quickly secrete a series of cytokines, thus activating other immune cells, in the physiological and pathological process plays an important role.
most of the iNKT cells are differentiated by double-positive thymus cells (CD4 plus CD8 plus) and the differentiation and maturation process is divided into four stages (phase 0-3).
stage 0 to stage 1, iNKT cells enter the rapid proliferation phase, stage 1 to stage 2 increase CD44 expression, obtain effect memory, stage 2 to stage 3, increase NK1.1 expression, become functionally mature iNKT cells.
phase 2 to stage 3 is the final stage of iNKT cell differentiation, which is critical to the establishment of iNKT cell-specific immune function, however, the molecular mechanism of regulating the differentiation phase has been unclear. The work of the
Liu Xiaolong Research Group revealed that after the specific knockout of the transcription medium sub-Med23 in mouse T cells, the differentiation of iNKT cells was completely stagnant at stage 2, which provided a new model for studying the end-of-life differentiation of iNKT cells.
compared the iNKT cell transcription groups of wild stages 2 and 3, and found that iNKT cells in stages 2 and 3 had different transcription regulation and the expression of immune function-related genes. Further functional analysis of the
showed that the iNKT cells of stage 3 could not only raise a series of NK cell-related surface receptors compared to phase 2 cells, but also had the ability to quickly secrete cytokines and chemofactors after being stimulated by antigens.
however, Med23's missing iNKT cell function is impaired, even can not reach the functional level of the iNKT cell in the wild type stage 2, showing insensitivity to antigen response, loss of immune cell recruitment ability, and ultimately lead to the ability of iNKT cells to remove tumors.
their study further revealed that the expression of AP-1 family transcription factor c-Jun in med23-defected iNKT cells could partially save the differentiation defects of iNKT cells.
this study in-depth discussion of the mechanism of the establishment of immune function in iNKT cells from stage 2 to stage 3, and reveals the role and mechanism of Med23 regulation of iNKT cell differentiation at the end of the stage.
is studying Ph.D. student Xu Wei as the first author of the paper, and researcher Liu Xiaolong is the author of the newsletter.
the study was helped by researchers Wu Ligang and his students Li Ronghong and Zhang Hongdao in transcription group sequencing.
the research was funded by the National Natural Science Foundation of China, the Chinese Academy of Sciences, the Youth Innovation Promotion Association of the Chinese Academy of Sciences and the China Postdoctoral Science Foundation, as well as the technical support of the Animal Experimental Technology Platform and the Cell Biology Technology Platform of the Public Technical Service Center of the Institute of Biochemistry and Cell.
Source: Shanghai Institute of Life Sciences.