Eosinophil diversity in asthma

Hulst, Glenn Van; Batugedara, Hashini Maneesha; Jorssen, Joseph; Louis, Renaud; Bureau, Fabrice; Desmet, Christophe

doi:10.1016/j.bcp.2020.113963

Cited by 31 publications

(29 citation statements)

References 85 publications

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“…This gure shows some key representative eosinophil molecules and not a complete list. responsiveness to cytokines (e.g., priming), prolonged survival for weeks, and various degrees of cellular activation (4,(32)(33)(34)(35). Additionally, eosinophils are capable of expressing diverse sets of proteins (e.g., surface markers, cytokines), mRNA transcripts, and lipids in response to different stimuli; in addition they release speci c granule proteins (Figure 1).…”

Section: Eosinophil Pleiotropy and Heterogeneitymentioning

confidence: 99%

Eosinophil Knockout Humans: Uncovering the Role of Eosinophils Through Eosinophil-Directed Biological Therapies

Jacobsen

Jackson

Heffler

et al. 2021

Annu. Rev. Immunol.

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The enigmatic eosinophil has emerged as an exciting component of the immune system, involved in a plethora of homeostatic and inflammatory responses. Substantial progress has been achieved through experimental systems manipulating eosinophils in vivo, initially in mice and more recently in humans. Eosinophil knockout mice have identified a contributory role for eosinophils in basal and inflammatory processes and protective immunity. Primarily fueled by the purported proinflammatory role of eosinophils in eosinophil-associated diseases, a series of anti-eosinophil therapeutics have emerged as a new class of drugs. These agents, which dramatically deplete eosinophils, provide a valuable opportunity to characterize the consequences of eosinophil knockout humans. Herein, we comparatively describe mouse and human eosinophil knockouts. We put forth the view that human eosinophils negatively contribute to a variety of diseases and, unlike mouse eosinophils, do not yet have an identified role in physiological health; thus, clarifying all roles of eosinophils remains an ongoing pursuit. Expected final online publication date for the Annual Review of Immunology, Volume 39 is April 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Section: Eosinophil Pleiotropy and Heterogeneitymentioning

confidence: 99%

Eosinophil Knockout Humans: Uncovering the Role of Eosinophils Through Eosinophil-Directed Biological Therapies

Jacobsen

Jackson

Heffler

et al. 2021

Annu. Rev. Immunol.

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“…The latter subgroup was also characterized by a minor content in granules and a greater response to activating stimuli in terms of survival, adhesion, oxygen metabolism, superoxide production, and antibody-dependent cytotoxicity. It is still debated whether the eosinophils in the lung can be considered as a distinct population from the circulating ones, although available evidence revealed differences between lung eosinophils and circulating cells, with the former displaying lower density, responsiveness, and surface marker expression [ 17 ].…”

Section: T2 High Mechanismsmentioning

confidence: 99%

The Role of Dupilumab in Severe Asthma

2021

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Dupilumab is a fully humanized monoclonal antibody, capable of inhibiting intracellular signaling of both interleukin (IL)-4 and IL-13. These are two molecules that, together with other proinflammatory cytokines such as IL-5 and eotaxins, play a pivotal role in orchestrating the airway inflammatory response defined as Type 2 (T2) inflammation, driven by Th2 or Type 2 innate lymphoid cells, which is the major feature of the T2 high asthma phenotype. The dual inhibition of IL-4 and IL-13 activities is due to the blockade of type II IL-4 receptor through the binding of dupilumab with the subunit IL-4Rα. This results in the repression of STAT6 and in the suppression of subsequent de novo formation of several molecules involved in the T2 inflammatory signature. Several clinical trials tested the efficacy and safety of dupilumab in large populations of uncontrolled severe asthmatics, revealing significant improvements in lung function, asthma control, and exacerbation rate. Similar results were reported when dupilumab was employed in patients harboring pathogenetic processes related to T2 immune response, such as atopic dermatitis and chronic rhinosinusitis. In this review, we provide an overview of the recent research in the field of respiratory medicine about dupilumab mechanism of action and its effects.

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“…As a cautionary note, we need to stress that the reciprocal translation of murine and human observations of eosinophil endotyping may not be entirely straightforward in our current state of knowledge [ 105 ]. We acknowledge that it may be tempting to directly relate murine inflammatory eosinophils to human hypodense eosinophils.…”

Section: Eosinophil Endotypes or Local Plasticity As Potential Effectors In Seamentioning

confidence: 99%

Eosinophils as Drivers of Severe Eosinophilic Asthma: Endotypes or Plasticity?

Hulst

Bureau

2021

IJMS

Self Cite

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Asthma is now recognized as a heterogeneous disease, encompassing different phenotypes driven by distinct pathophysiological mechanisms called endotypes. Common phenotypes of asthma, referred to as eosinophilic asthma, are characterized by the presence of eosinophilia. Eosinophils are usually considered invariant, terminally differentiated effector cells and have become a primary therapeutic target in severe eosinophilic asthma (SEA) and other eosinophil-associated diseases (EADs). Biological treatments that target eosinophils reveal an unexpectedly complex role of eosinophils in asthma, including in SEA, suggesting that “not all eosinophils are equal”. In this review, we address our current understanding of the role of eosinophils in asthma with regard to asthma phenotypes and endotypes. We further address the possibility that different SEA phenotypes may involve differences in eosinophil biology. We discuss how these differences could arise through eosinophil “endotyping”, viz. adaptations of eosinophil function imprinted during their development, or through tissue-induced plasticity, viz. local adaptations of eosinophil function through interaction with their lung tissue niches. In doing so, we also discuss opportunities, technical challenges, and open questions that, if addressed, might provide considerable benefits in guiding the choice of the most efficient precision therapies of SEA and, by extension, other EADs.

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Eosinophil diversity in asthma

Cited by 31 publications

References 85 publications

Eosinophil Knockout Humans: Uncovering the Role of Eosinophils Through Eosinophil-Directed Biological Therapies

Eosinophil Knockout Humans: Uncovering the Role of Eosinophils Through Eosinophil-Directed Biological Therapies

The Role of Dupilumab in Severe Asthma

Eosinophils as Drivers of Severe Eosinophilic Asthma: Endotypes or Plasticity?

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