Transcriptional Regulatory Network for the Development of Innate Lymphoid Cells

Figure 1

Parallels between the development of innate lymphocytes and T cells. Lymphoid DCs, B cells, T cells, and innate lymphocytes including ILCs and cNK cells are derived from common lymphoid progenitors (CLPs). While innate lymphocytes mainly develop in the bone marrow, T cells develop in the thymus. T cell development passes through a fate determination (from ETP/DN1 to DN2 to DN3) stage before CD4⁺ and CD8⁺ T cells develop separately from progenitor-like CD4⁺CD8⁺ DP cells. After CD4⁺ T cell development, effector Th cells are differentiated from naïve CD4⁺ T cells upon activation. In parallel, for the innate lymphocyte development, there may also be a stage when the innate fate is determined followed by the generation of ILC and cNK common progenitors. ILC and cNK lineage then develop separately under the guidance of distinct master regulators. Similar to effector Th cells differentiating from naïve CD4⁺ T cells, all mature ILC subsets also develop from a common progenitor. Therefore, ILCs share with T cells in utilizing multiple transcription factors at similar stages during their development/differentiation.