Research Article: Comparison of IL-33 and IL-5 family mediated activation of human eosinophils

Date Published: September 6, 2019

Publisher: Public Library of Science

Author(s): Evelyn L. Angulo, Elizabeth M. McKernan, Paul S. Fichtinger, Sameer K. Mathur, Svetlana P. Chapoval.

http://doi.org/10.1371/journal.pone.0217807

Abstract

Eosinophils are the prominent inflammatory cell involved in allergic asthma, atopic dermatitis, eosinophilic esophagitis, and hypereosinophilic syndrome and are found in high numbers in local tissue and/or circulating blood of affected patients. There is recent interest in a family of alarmins, including TSLP, IL-25 and IL-33, that are epithelial-derived and released upon stimulation of epithelial cells. Several genome wide association studies have found SNPs in genes encoding IL-33 to be risk factors for asthma. In two studies examining the direct role of IL-33 in eosinophils, there were differences in eosinophil responses. We sought to further characterize activation of eosinophils with IL-33 compared to activation by other cytokines and chemokines. We assessed IL-33 stimulated adhesion, degranulation, chemotaxis and cell surface protein expression in comparison to IL-3, IL-5, and eotaxin-1 on human eosinophils. Our results demonstrate that IL-33 can produce as potent eosinophil activation as IL-3, IL-5 and eotaxin-1. Thus, when considering specific cytokine targeting strategies, IL-33 will be important to consider for modulating eosinophil function.

Partial Text

Eosinophils are the prominent immune cells involved in allergic asthma, atopic dermatitis, eosinophilic esophagitis, and hypereosinophilic syndrome and are found in high numbers in local tissue and/or circulating blood of affected patients [1]. In the tissue, eosinophils can release toxic granule contents including Major Basic Protein (MBP), Eosinophil Derived Neurotoxin (EDN), and Eosinophil Peroxidase (EPX), which may cause intended damage to the target in the case of parasitic infections, but can inadvertently damage surrounding host tissue and trigger remodeling. In severe asthma, this can lead to chronic inflammation of the airway resulting in long-term injury and remodeling. In addition, we and others have demonstrated that eosinophils are pro-inflammatory cells signaling other immune cells through cytokine release especially by driving and propagating the Th2 type immune response [2, 3].

Our results demonstrate that IL-33 is as potent as IL-3 and IL-5 in inducing eosinophil adhesion and EDN degranulation. In addition, eosinophil stimulation with IL-33 resulted in increased expression of the cell surface markers CD11b, CD18, CD66b, and ICAM-1 in a manner comparable to that of IL-3, IL-5, and eotaxin-1. Our study confirms the lack of chemotaxis from IL-33 stimulation. Few studies have examined the comparative effects of IL-33 vs. IL-3, IL-5 or eotaxin-1 on eosinophils. To our knowledge, increased eosinophil expression of CD18 and CD66b after IL-33 stimulation has not previously been described.

 

Source:

http://doi.org/10.1371/journal.pone.0217807

 

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