Innate Lymphoid Cells


Innate lymphoid cells (ILCs) are white blood cells derived from a common progenitor in the bone marrow. They respond rapidly to a limited array of antigens at the site of infection to provide immediate protection. The first identified ILCs were natural killer cells. However, several non‐cytotoxic members of the family have since been reported. All ILCs lack the rearranged antigen receptors characteristic of T‐ and B‐cells but can be similarly divided into three main groups based on cell surface markers and cytokine expression profiles. Similar to their adaptive immune response counterparts, they play specific roles in providing host defence against different pathogens. In addition, there is growing evidence that ILCs can contribute to multiple inflammatory and autoimmune diseases.

Key Concepts

  • ILCs are lymphocytes of the innate immune system and provide a rapid response to invading pathogens.
  • ILCs lack the specific antigen receptors found on cells of the adaptive immune system.
  • Development of ILCs is governed by sequential expression of different transcription factors and proceeds from a common precursor found in the bone marrow.
  • Differential expression of cell surface markers and cytokines allows ILCs to be grouped into three families, each having a different role in host immunity.
  • ILCs respond to signals released from epithelial and other cells to provide a rapid source of cytokines that can recruit other immune cells and stimulate tissue repair.
  • The dysregulation of ILC activation has been linked to several human inflammatory and autoimmune diseases.

Keywords: lymphocytes; innate immunity; cytokines; transcriptional regulation; inflammation; ILCs

Figure 1. Categorisation of innate lymphoid cells is based on cytokine expression and falls into three groups. ILC, innate lymphoid cell; IFNγ, interferon‐γ; LTI, lymphoid tissue inducer cell; NCR, natural cytotoxicity receptor; NK, natural killer and TSLP, thymic stromal lymphopoietin.
Figure 2. Transcription factor expression directs the development of lymphocytes from a common precursor. Black arrows indicate transcription factor expression. AHR, aryl hydrocarbon receptor; CLP, common lymphocyte progenitor; ILC, innate lymphoid cell; LTI, lymphoid tissue inducer cell; NK, natural killer; PLZF, pro‐myeloid leukaemia zinc finger and ROR, RAR‐related orphan receptor.
Figure 3. The role of group 1 innate lymphoid cells (ILCs) in protection against intracellular pathogens. Infected epithelial cells release IL‐12 and IL‐15, which stimulate ILC1s and natural killer (NK)‐cells to release mediators including interferon‐γ (IFNγ) to attract and activate macrophages, and monocytes. In addition, IL‐15 enhances the granzyme/perforin‐mediated killing by NK‐cells.
Figure 4. Innate lymphoid cells (ILCs) of group 2 are central to coordinate expulsion of large, extracellular parasites such as helminths. ILC2s respond to the release of IL‐33, IL‐25 and thymic stromal lymphopoietin (TSLP) to release large quantities of type 2 cytokines including IL‐13 which stimulates goblet cells to produce mucus and IL‐5 to recruit eosinophils. Several feedback loops exist between adaptive immune cells and the ILC2s to maintain the response. PGD2, prostaglandin D2.
Figure 5. Type 3 innate lymphoid cells (ILCs) protect cells from extracellular pathogens including bacteria and fungi. IL‐22 is released from ILC3s in response to IL‐23 and IL‐1β secreted by gut epithelial cells. IL‐22 directly acts on the epithelium to regulate matrix metalloproteinase (MMP) expression and maintain barrier integrity. In the lung, ILC3s induce inflammatory mediator production and prevent fungal colonisation through the release of IL17A.


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Further Reading

Artis D and Spits H (2015) The biology of innate lymphoid cells. Nature 517: 293–301.

McKenzie ANJ, Spits H and Eberl G (2014) Innate lymphoid cells in inflammation and immunity. Immunity 41: 366–374.

Spits H and Cupedo T (2012) Innate lymphoid cells: emerging insights in development, lineage relationships, and function. Annual Review of Immunology 30: 647–675.

Walker JA and McKenzie ANJ (2013) Development and function of group 2 innate lymphoid cells. Current Opinion in Immunology 25: 148–155.

Wan YY (2014) GATA3: a master of many trades in immune regulation. Trends in Immunology 35: 233–242.

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How to Cite close
Cousins, David J, and Weston, Cathryn(Nov 2015) Innate Lymphoid Cells. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0026245]