Immunity . . . The Zhong Chao/Zhu Jinfang collaboration reveals the genealogical determining mechanism in the development of inherent lymphocytes.

Innate lymphocyte (ILC) is a kind of lymphocyte that does not express specific antigen recognition receptors (such as TCR and BCR).their functional characteristics correspond to T lymphocytes in the acquired immune system, and they are divided into three subgroups: ilc1, ilc2 and ilc3 according to their different expression of transcription factors and production of helper cytokines.most ILCs reside in mucosal tissues and play an important role in regulating the immune balance of tissues, resisting pathogen infection, and enhancing the acquired immune response mediated by T and B cells.in the past decade, the discovery and functional research of ILC have greatly enhanced our understanding of the immunoregulation in mucosal tissue.however, there are still controversies about the development process and phylogenetic classification of the three ILC subgroups.in 2014, diefenbach Laboratory of meinz University in Germany and bendelac Laboratory of University of Chicago in the United States almost simultaneously reported two kinds of precursor cells in the development of ILC on cell and nature respectively.the former found that a group of common helper like innate lymphid promoter (chilp) which expressed high level of Id2 in mouse bone marrow could produce all ILC subsets.however, another group of ILC precursor cells found by the latter expressed high-level transcription factor PLZF, which produced ILC different from chilp. In the three subgroups of ILC,ILC can be further divided into two groups, one group of which expresses CCR6 on the surface, which is called lymphoid tissue They are necessary for the formation of secondary lymphoid structures (such as lymph nodes, Peyer's lymph nodes, etc.) and play an important role in acquired immunity.plzfhigh ILC precursor cells could not produce LTI, but all other ILC could be produced.this raises the question whether LTI is the same as other ILCs in genealogical origin. However, the deletion of PLZF (zbtb16 coding) did not cause obvious ILC development defects, and some studies have shown that LTI is very similar to other ilc3 in immune function, which makes it lack of evidence to classify LTI and non LTI ILC according to PLZF which has no effect on the development process.it is of great significance to explore the development process and regulatory mechanism of each subgroup of ILC, and to understand the relationship between innate immunity and acquired immunity in the evolutionary process.on December 24, 2019, the team of Zhong Chao of Peking University and Zhu JinFang, a senior researcher of NIH, published the results of differential expression of the transcription factor GATA3 specifications lineage and functions of innate lymphoma cells in the development of ILC ILC plays an important role in determining its fate.researchers previously reported that GATA3 is an essential transcription factor for all ILC development (Yagi & amp; Zhong et al. Immunity, 2014).based on this, this study further found that there were some residual LTI in the peripheral tissues of GATA3 deficient mice (gata3fl / flvavcre), while all other ILC subpopulations did not exist, indicating that LTI was significantly different from other ILCs in the development process.further analysis of the effect of GATA3 deletion on ILC precursor cells showed that plzfhigh ILC precursor cells did not exist in the mice, but there were still some residual chilp cells, which was consistent with the above-mentioned ILC production in peripheral tissues.next, this study analyzed the difference of GATA3 expression in ILC precursor cells.the researchers first revised the definition of chilp cells (rchilp) according to the latest understanding of ILC development.the expression of GATA3 and Id2 in rchilp was obviously heterogeneous, which could be divided into three groups according to their expression levels: gata3highid2igh, gata3lowid2igh and id2low.according to the results of surface marker detection and transplantation development experiment, gata3high rchilp corresponds to plzfhigh ILC precursor cells previously reported, and gata3low rchilp corresponds to LTI precursor cells.in order to further explain the difference of rchilp caused by different GATA3 expression levels, the researchers further analyzed the expression of 92 important genes in rchilp single cell by using single cell multiplex qPCR technology.the results showed that the single cell clustering based on the expression of these 92 genes was basically consistent with the above classification of rchilp groups according to the expression levels of GATA3 and Id2. Moreover, the expression of GATA3 was significantly positively correlated with the expression of non LTI ILC lineage related genes, which further demonstrated the important influence of GATA3 expression level on the fate formation of non LTI ILC lineage.in addition to GATA3, transcription regulators Id2 and IL-7 and IL-15, members of the cytokine IL-2 family, are also important for the production of all ILCs.the researchers found that only GATA3 has a decisive role in the lineage fate differentiation of LTI and non LTI ILC.Id2 mainly promotes the differentiation of ILC into mature cells, while IL-7 and IL-15 have no effect on the production of precursor cells during the development of ILC.to sum up, GATA3 is the only known functional molecule that can distinguish the lineage of LTI and non LTI ILC, and its expression level determines the fate differentiation of these two lineages during the development of ILC.previously, all ILCs were generally referred to as innate lymphocytes corresponding to CD4 + helper T cells. According to the degree of dependence on GATA3 during development and the expression level of GATA3 in its precursor cells, non LTI ILC is the real ILC corresponding to CD4 + helper T cells.the functional differences between LTI and non LTI ILC need to be further explored.Dr. Zhong Chao completed the postdoctoral training in the NIH Zhu JinFang research group. During this period, his work systematically revealed the important transcriptional regulation role of GATA3 in various stages of ILC.and returned to China in 2017 to join the Institute of Systems Biomedicine, Peking University, mainly studying the immune regulation mechanism of mucosal tissue.at present, there is still a vacancy in the post doctoral position of the laboratory. Please write to us（ zhongc@hsc.pku.edu.cn ）Consultation.original link: plate maker: Ke