Innate Lymphoid Cell Differentiation Pathways

Click on a cell type below to view a subset of molecules used as markers for the identification of that cell type.

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Common Lymphoid
Progenitor
Common Lymphoid
Progenitor
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Common Lymphoid
Progenitor
Common Lymphoid
Progenitor
IL-7
IL-7
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IL-15
IL-15
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Natural Killer
Cell Precursor
Natural Killer
Cell Precursor
IL-2
IL-2
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IL-12
IL-12
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Immature
NK Cell
Immature
NK Cell
IL-12
IL-12
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IL-18
IL-18
Mature
NK Cell
Mature
NK Cell
Cytotoxic
NK Cell
Cytotoxic
NK Cell
Immunoregulatory
NK Cell
Immunoregulatory
NK Cell
IL-7
IL-7
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Lymphoid Tissue
Inducer Progenitor
Lymphoid Tissue
Inducer Progenitor
IL-1 beta
IL-1 beta
IL-23
IL-23
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Lymphoid Tissue
Inducer Cell
Lymphoid Tissue
Inducer Cell
ILC
Progenitor
ILC
Progenitor
IL-7
IL-7
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Immature
ILC2
Immature
ILC2
IL-25
IL-25
IL-33
IL-33
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TSLP
TSLP
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ILC2
ILC2
IL-12
IL-12
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IL-18
IL-18
ILC1
ILC1
IL-12
IL-12
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IL-15
IL-15
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IEL
IEL
IL-7
IL-7
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IL-1 beta
IL-1 beta
IL-23
IL-23
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NCR-
ILC3
NCR-
ILC3
IL-2
IL-2
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IL-12
IL-12
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ILC1
ILC1
IL-2
IL-2
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IL-23
IL-23
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NCR+
ILC3
NCR+
ILC3
Secreted
Cytokines
Secreted
Cytokines
Secreted
Cytokines
Secreted
Cytokines
Secreted
Cytokines
Secreted
Cytokines
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Secreted
Cytokines
Secreted
Cytokines
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Secreted
Cytokines
Secreted
Cytokines
Secreted
Cytokines
Secreted
Cytokines
Secreted
Cytokines
Secreted
Cytokines
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Secreted
Cytokines
Secreted
Cytokines
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Secreted
Cytokines
Secreted
Cytokines

Overview of Innate Lymphoid Cells Differentiation

Innate Lymphoid Cells (ILCs) are a newly-identified subset of hematopoietic effector cells. ILCs are implicated in the preservation of epithelial integrity of the gut, the lung and the skin, and also participate in immune responses against pathogens through rapid and potent cytokine production. All ILC populations develop from a common lymphoid progenitor (CLP), which is localized to the fetal liver or adult bone marrow. Expression of the transcription factor ID2 (inhibitor of DNA binding) triggers CLP differentiation into the ILC pathway. ID2-dependent progenitors are directed towards particular ILC phenotypes through the expression of lineage-specific transcription factors. Because ILCs share developmental and functional similarities with helper T (Th) cells, a nomenclature for ILCs has been established based on Th cell classification. ILCs are categorized into three groups according to the transcription factors mediating their development and the cytokines they secrete. Group-1 ILCs are under the control of the T-bet transcription factor and include natural killer (NK) cells and ILC1 cells. These cells secrete type-1 cytokines such as IFN-gamma and TNF-alpha in response to intracellular pathogens. Group-2 ILCs rely on the GATA-3 and ROR-alpha transcription factors and produce type-2 cytokines (IL-5, IL-9, IL-13) in response to extracellular parasite infections. Finally, Group-3 ILCs, such as Lymphoid Tissues inducer cells (LTi) and ILC3 cells, are under the control of the ROR-gamma t transcription factor and produce IL-17 and/or IL-22. LTi cells are required for the development of lymphoid tissues, while ILC3 cells mediate the balance between intestinal symbiotic microbiota and immunity. The pathway depicted below represents the differentiation of innate lymphoid cells and identifies essential markers that enable precise identification and categorization of each ILC type.

To learn more, please visit our Innate Lymphoid Cells (ILCs) Research Area.

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