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. 2022 Jan;128(1):53-60.e3.
doi: 10.1016/j.anai.2021.08.004. Epub 2021 Aug 12.

Interleukin-5 receptor alpha (CD125) expression on human blood and lung neutrophils

Monica G Lawrence  1 , W Gerald Teague  2 , Xin Feng  3 , Caitlin Welch  4 , Elaine Etter  4 , Julie Negri  4 , Marthajoy Spano  5 , Kristin Wavell  2 , Thomas Braciale  6 , John W Steinke  7 , Larry Borish  8
Affiliations

Interleukin-5 receptor alpha (CD125) expression on human blood and lung neutrophils

Monica G Lawrence et al. Ann Allergy Asthma Immunol. 2022 Jan.

Abstract

Background: Our previous studies revealed the presence of interleukin-5 (IL-5) receptor alpha chain (IL-5Rα, CD125) on neutrophils in a murine model of influenza and in the lung fluid of children with severe asthma.

Objective: To further evaluate the functional characteristics and effects of clinical factors and inflammatory variables on neutrophil surface IL-5Rα abundance in lung fluid and blood.

Methods: IL-5Rα expression was quantified by flow cytometry performed on purified neutrophils from blood and bronchoalveolar lavage fluid samples obtained from healthy controls and individuals with asthma. Expression was further confirmed by immunohistochemistry. Functional signaling through the IL-5Rα was evaluated by measurement of IL-5-inducible modulation of neutrophil surface CD62L and IL-5Rα expression.

Results: IL-5Rα was consistently present but at a variable magnitude on blood and lung neutrophils. Expression on lung neutrophils was significantly higher than that on blood cells (p"?>P < .001) where their expression was higher in the presence of airway pathogens, especially with respiratory viruses. Increased receptor expression occurred in response to the translocation of preformed receptors from intracellular stores. Receptors were functional as revealed by IL-5-mediated down-regulation of CD62L and the feed-forward up-regulation of reception expression.

Conclusion: In addition to the expression on eosinophils and basophils, the IL-5Rα is consistently and abundantly expressed on the surface of blood and especially air space neutrophils. These observations support the concept that some of the efficacy of IL-5/IL-5R-targeting biologics observed in asthma may reflect their ability to target neutrophilic air space inflammation.

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Conflict of interest statement

Conflict of Interest: Dr. Larry Borish was the recipient of an investigator-initiated medical school grant from Astra Zeneca which funded parts of these studies. All funds were transmitted to the University of Virginia. None of the other authors have relevant COIs to report.

Figures

Figure 1.
Figure 1.. Comparison of blood and lung neutrophil CD125 expression.
A. Scatter plot of surface neutrophil CD125 abundance in the BAL and blood of children with severe asthma. B. Immunohistochemistry of non-permeabilized blood neutrophils (top) and eosinophils (bottom) examined for surface CD125 (right panels). Also shown are isotype controls (left panels). C. Scatter plot showing paired relationships between BAL and blood neutrophil surface CD125. D. Scatter plot of total (surface and intracellular) neutrophil CD125 abundance in the BAL and blood of children with severe asthma
Figure 2.
Figure 2.. Lung neutrophil CD125 expression.
A. Violin plots showing the log10 BAL neutrophil (PMN) surface CD125 abundance compared according to four categorical BAL granulocyte patterns. B. Component plot in three dimensions utilizing rotated factor loads based on the correlation of clinical outcome variables.
Figure 3.
Figure 3.. Influences on lung neutrophil CD125 expression.
Violin plot of BAL neutrophil CD125 surface abundance in children A. with/without viral transcripts in BAL; B. with/without rhinovirus transcripts in BAL; C. with/without BAL eosinophilia. D. Scatter plot with advancing age and BAL neutrophil CD125 abundance.
Figure 4.
Figure 4.. Activation of neutrophils.
A. Neutrophils were stimulated with IL-5, fMLP/cytochalasin b, or PMA/ionomycin for 15 min and surface expression of CD125 quantified by flow cytometry. B. Neutrophils were stimulated with IL-5 or fMLP/cytochalasin b and surface expression of CD62L quantified via flow cytometry. *p<0.05, ***p<0.01.
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