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  • Review Article
  • Published:

Functions of tissue-resident eosinophils

Nature Reviews Immunology volume 17, pages 746–760 (2017)Cite this article

Subjects

Key Points

  • Eosinophils, as cells of the innate immune system and sources of diverse cytokines, function in diverse tissue sites, some previously unappreciated, in health and disease.

  • At least in human eosinophils, many cytokine proteins are present preformed and stored within eosinophil cytoplasmic granules.

  • Eosinophil secretion of cytokines can occur by regulated transport of granule-derived proteins through the vesicular transport system to enable extracellular release. The relative contributions to eosinophil cytokine secretion of preformed granule stores, de novo transcription and mRNA transcript stabilization remain to be determined.

  • The signalling mechanisms within eosinophils that regulate the selective secretion of specific cytokines remain to be elucidated.

  • Eosinophil-secreted cytokines can contribute to immune and metabolic homeostasis, as well as having roles in tissue regeneration, wound healing and host defence.

Abstract

Eosinophils are a prominent cell type in particular host responses such as the response to helminth infection and allergic disease. Their effector functions have been attributed to their capacity to release cationic proteins stored in cytoplasmic granules by degranulation. However, eosinophils are now being recognized for more varied functions in previously underappreciated diverse tissue sites, based on the ability of eosinophils to release cytokines (often preformed) that mediate a broad range of activities into the local environment. In this Review, we consider evolving insights into the tissue distribution of eosinophils and their functional immunobiology, which enable eosinophils to secrete in a selective manner cytokines and other mediators that have diverse, 'non-effector' functions in health and disease.

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Figure 1: Eosinophil-derived mediators and their functions.
Figure 2: Modes of eosinophil secretion.
Figure 3: Ultrastructure of activated human eosinophils and immunolocalization of mobilized MBP1 and IL-4.

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Acknowledgements

We acknowledge the many investigators who have provided contributions to understanding the immunobiology of eosinophils, and we note that space constraints limited our citations. For electron microscopy studies specifically, the expertise of A. M. Dvorak and R. C. Melo has been crucial in revealing ultrastructure-based insights into eosinophil secretion mechanisms. Our studies have been supported by US National Institutes of Health grants R37AI020241, R01AI022571 and R01HL051645 (to P.F.W.), and R01HL095699 and R01AI121186 (to L.A.S.).

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Authors and Affiliations

  1. Division of Allergy and Inflammation, Harvard Medical School, Beth Israel Deaconess Medical Center, CLS 943, 330 Brookline Avenue, Boston, 02215, Massachusetts, USA

    Peter F. Weller & Lisa A. Spencer

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  1. Peter F. Weller
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  2. Lisa A. Spencer
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Both authors contributed equally to researching data for the article, discussion of content, and writing, reviewing and editing the manuscript before submission.

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Correspondence to Peter F. Weller.

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PowerPoint slides

Glossary

Side scatter (SSC) parameter

In flow cytometry, the SSC parameter is a measurement of light scatter taken at a ninety-degree angle relative to the laser. As cellular components such as granules increase the light refraction, SSC is a useful parameter to distinguish cell populations on the basis of their cellular complexity.

Eosinophil-like cell lines

The cell lines HL-60 clone 15 and EoL-1 were derived from the blood of patients with acute promyelocytic or eosinophilic leukaemia, respectively. When cultured under specific conditions, these cell lines can be differentiated into cells with cytological and functional features of eosinophils.

Type 1 cytokines

Cytokines typically produced by T helper 1 cells, including IL-2, interferon-γ and IL-12.

Type 2 cytokines

Cytokines typically produced by T helper 2 cells, including IL-4, IL-5, IL-6, IL-10 and IL-13.

Intragranular membrano-vesicular network

Intricate network of interconnected vesicular tubules that is evident within eosinophil granules undergoing piecemeal degranulation. These tubules are thought to give rise to granule-derived secretory vesicles.

Eosinophilic oesophagitis

Chronic allergic inflammatory disease characterized by the accumulation of a large number of eosinophils in the oesophagus, an organ that is normally devoid of eosinophils.

Immunonanogold localization

Electron microscopy technique using antibodies conjugated to very small (1.4 nm) gold particles to enable subcellular localization of proteins.

Eosinophil sombrero vesicles

(EoSVs). C-Shaped tubular vesicles that are named in recognition of their similarity in cross-sectional appearance in electron micrographs to a Mexican hat.

Group 2 innate lymphoid cells

(ILC2s). ILCs are innate immune cells that derive from common lymphoid progenitors and are considered part of the lymphoid lineage. ILC2s produce cytokines associated with T helper 2 cells (such as IL-4, IL-5 and IL-13).

4get mice

Bicistronic IL-4 reporter mice were generated by the targeted addition of an internal ribosomal entry site–enhanced green fluorescent protein (IRES–eGFP) to generate IL-4–GFP–enhanced transcript (4get) mice.

Alternatively activated M2 macrophages

Anti-inflammatory cells that function in tissue repair and remodelling. M2 macrophages are characterized by the production of IL-10 and transforming growth factor-β.

Classically activated M1 macrophages

Macrophages that are activated by lipopolysaccharide and interferon-γ to secrete high levels of IL-12 and produce nitric oxide, promoting a pro-inflammatory antimicrobial response.

Mitochondrial brown fat uncoupling protein 1

Also known as thermogenin. This protein spans the inner mitochondrial membrane and functions as a proton transporter, thereby uncoupling the proton gradient that is produced during oxidative phosphorylation from ATP production, causing the chemical energy to instead be dissipated as heat.

Beige adipocytes

Adipocytes that express uncoupling protein 1 and have thermogenic capacity. They are induced in white adipose tissue by cold either directly or indirectly through activation of the β-adrenergic signalling pathway.

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Weller, P., Spencer, L. Functions of tissue-resident eosinophils. Nat Rev Immunol 17, 746–760 (2017). https://doi.org/10.1038/nri.2017.95

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