GATA3 quantitatively specifies the lineage fates of innate lymphoid cells
作者单位：Institute of Systems BiomedicineSchool of Basic Medical SciencesPeking University Health Science Center Molecular and Cellular Immunoregulation UnitLaboratory of ImmunologyNational Institute of Allergy and Infectious DiseasesNational Institutes of Health
会议名称：《第十三届全国免疫学学术大会》
会议日期：2018年
学科分类：1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学]
关 键 词：ILC LTi lineage specification GATA3 Id2
摘 要：Innate lymphoid cells(ILCs) corresponds the innate counterpart of CD4T helper cells given their paralleled functions. Current studies also revealed the similarity of development between these two lymphoid lineages. While the regulatory function of GATA3 during CD4 T cell development have been understudied, how GATA3 regulates different ILC progenitors is far from clear. Lymphoid tissue inducer(LTi) cells are a very earliest discovered ILC population, but a recent study tracing PLZF expression during ILC generation had shown that they developed in a distinct way from other ILCs. Here, we also found that the LTi cell development was independent of GATA3. In the opposite, the PLZF-expressing progenitors that give rise to other ILCs were completely absent under Gata3 deficiency. Moreover, the PLZFILC progenitor and the LTi progenitor also showed quantitative difference on GATA3 expression. While a GATA3 subset within previously reported common progenitors for all helper-like innate lymphocytes(ChILPs) is found consistent with the PLZF ILC progenitors in generating all non-LTi ILCs, the residual GATA3 subset is mainly composed of the GATA3-independent LTi progenitors, most of which also express RORγt and CCR6. A single cell gene expression analysis also confirmed these differences between the progenitors for LTi and other ILCs. Moreover, in the PLZF ILC progenitors, GATA3 expression positively correlate with most of its lineage specific genes, while negatively correlated with certain LTi lineage specific genes. Thus, GATA3 level in the ILC progenitors fundamentally dictates their developments.