A hidden residential cell in the lung
Marc E. Rothenberg
Marc E. Rothenberg
Published September 1, 2016; First published August 22, 2016
Citation Information: J Clin Invest. 2016;126(9):3185-3187. https://doi.org/10.1172/JCI89768.
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Category: Commentary

A hidden residential cell in the lung

Abstract

Eosinophils are classically known as proinflammatory cells, as they are equipped with a variety of preformed cytotoxic mediators and have been shown to definitively contribute to asthma. The connection between eosinophils and asthma development has led to a new class of asthma therapeutics based on blocking eosinophils with humanized antibodies that neutralize IL-5, a potent eosinophil growth, activation, and survival factor. Yet, recent studies have led to an increasing appreciation that eosinophils have a variety of homeostatic functions, including immunomodulation. In this issue of the JCI, Mesnil et al. identify a notable population of lung-resident eosinophils and demonstrate that, compared with traditional eosinophils, these cells have distinct characteristics, including nuclear structure, surface markers, IL-5 independence, and immunoregulatory function that is capable of polarizing adaptive immune responses, at least in vitro. Thus, these results reinforce a key homeostatic role for this enigmatic cell population, particularly in residing and regulating immunity in the lung.

Authors

Marc E. Rothenberg

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Figure 1

Schematic diagram of the homeostatic roles of eosinophils.

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Schematic diagram of the homeostatic roles of eosinophils. Eosinophils t...
Eosinophils transit through the blood stream and home into various tissues at baseline. This schematic focuses on three tissues — adipose, small intestine, and lung. In adipose tissue, eosinophils regulate glucose levels and metabolism via eosinophil-derived IL-4, which regulates macrophage polarization and subsequent generation of insulin-sensitizing agents. In the small intestine, eosinophils regulate secretory IgA, mucus production and microbiota composition. A study in this issue by Mesnil et al. (8) show that in the lung, there is a substantial population of rEos in the parenchyma. These eosinophils have a ringed nucleus and express differential levels of Siglec-F and CD62L compared with inflammatory eosinophils and also express cardinal eosinophil markers including CCR3 and CD123 (the IL-5 receptor). Lung rEos have putative immunosuppressive function. Please note that the data in this figure are mainly derived from murine studies.