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  • Review Article
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Heterogeneity of type 2 innate lymphoid cells

Nature Reviews Immunology volume 22, pages 701–712 (2022)Cite this article

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Abstract

More than a decade ago, type 2 innate lymphoid cells (ILC2s) were discovered to be members of a family of innate immune cells consisting of five subsets that form a first line of defence against infections before the recruitment of adaptive immune cells. Initially, ILC2s were implicated in the early immune response to parasitic infections, but it is now clear that ILC2s are highly diverse and have crucial roles in the regulation of tissue homeostasis and repair. ILC2s can also regulate the functions of other type 2 immune cells, including T helper 2 cells, type 2 macrophages and eosinophils. Dysregulation of ILC2s contributes to type 2-mediated pathology in a wide variety of diseases, potentially making ILC2s attractive targets for therapeutic interventions. In this Review, we focus on the spectrum of ILC2 phenotypes that have been described across different tissues and disease states with an emphasis on human ILC2s. We discuss recent insights in ILC2 biology and suggest how this knowledge might be used for novel disease treatments and improved human health.

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Fig. 1: The plasticity and migration of ILC2s generate phenotypic diversity in tissues.
Fig. 2: ILC2s can contribute to tumour rejection or tumour growth.
Fig. 3: ILC2s are involved in adipose tissue homeostasis.
Fig. 4: ILC2s are involved in virus-induced exacerbations of airway inflammation.

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Acknowledgements

The authors thank J. Bernink, K. Golabski and R. Stadhouders for helpful input on the manuscript.

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Authors and Affiliations

  1. Department of Experimental Immunology, Amsterdam UMC, Location AMC, University of Amsterdam, Amsterdam, Netherlands

    Hergen Spits

  2. Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

    Jenny Mjösberg

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The authors contributed equally to all aspects of the article.

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Correspondence to Hergen Spits or Jenny Mjösberg.

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H.S. is a consultant for GlaxoSmithKline. J.M. declares no competing interests.

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Nature Reviews Immunology thanks G. Eberl, N. Satoh-Takayama and R. Locksley for their contribution to the peer review of this work.

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Glossary

Alarmin

A type of damage-associated molecular pattern composed of endogenously produced proteins or peptides, including IL-33, that are released upon immune activation, degranulation, cell injury or death.

Chronic rhinosinusitis with nasal polyps

(CRSwNP). A chronic inflammation of sinonasal tissues, resulting in the formation of inflammatory lesions and polyps, and manifested as rhinorrhoea, nasal congestion, and facial pressure and/or pain.

Beiging

The process by which white adipose tissue is converted to a phenotype more similar to that of brown adipose tissue, thereby increasing energy expenditure by reducing lipids stored within the adipose tissue.

Enkephalins

Small peptides that function as neurotransmitters and that bind to opioid receptors.

Metabolic syndrome

A combination of conditions, including high blood pressure, high blood glucose levels, high levels of waist body fat, and high cholesterol or triglyceride levels, that predisposes for development of heart disease and type 2 diabetes.

Ketogenic diet

Dietary intake of high levels of fat and low levels of carbohydrate.

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Spits, H., Mjösberg, J. Heterogeneity of type 2 innate lymphoid cells. Nat Rev Immunol 22, 701–712 (2022). https://doi.org/10.1038/s41577-022-00704-5

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