
Innate lymphoid cells (ILCs) are a heterogeneous family of lymphocytes that lack conventional antigen receptors and play roles in tissue homeostasis and immune responses. Based on their transcriptional and functional properties, ILCs are classified into three main groups: group 1 ILCs (ILC1s and NK cells), group 2 ILCs (ILC2s), and group 3 ILCs (ILC3s). The developmental origins of ILCs remain an area of active investigation. Multiple progenitor populations contribute to their differentiation, including common innate lymphoid progenitors (CILPs), ILC-restricted progenitors, and IL-18 receptor-positive progenitors. Recent studies suggest that ILCs can arise from diverse pathways beyond BM-derived progenitors, including extramedullary sites such as the fetal lung and thymus. Thymic-derived ILC2s have been identified, suggesting an alternative route of development that challenges the traditional BM-centric model. This commentary discusses the current understanding of ILC development, emphasizing the contributions of BM progenitors, tissue-resident precursors, and alternative developmental pathways. Unraveling the regulatory mechanisms governing ILC differentiation will provide critical insights into their roles in immune surveillance and tissue-specific immunity.
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