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

Abstract

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.

Baseline Eosinophil Count as a Potential Clinical Biomarker for Clinical Complexity in EGPA: A Real-Life Experience

“…Although the pathogenesis of EGPA is a complex scenario, it is very likely that asthma and EGPA share common pathogenic aspects. It is well-known that asthma is frequently characterized by an increase in blood eosinophils that as well as releasing several mediators and cytokines, are also involved in tissue damage [ 28 , 29 , 30 ]. Therefore, over time, severe forms of eosinophilic asthma can evolve in EGPA.…”

Eosinophilic inflammation: An Appealing Target for Pharmacologic Treatments in Severe Asthma

“…The exact mechanisms underlying airway remodeling processes in eosinophilic asthma are not yet fully understood; however, elevated TGF-β1 levels in the airways of asthmatic patients suggest a possible role for eosinophils [ 95 , 96 ], which are one of the main sources of TGF-β1 and after their activation by IL-5 [ 15 , 96 ] are able to release large amounts of TGF-β1 at the site of inflammation [ 97 ]. Furthermore, eosinophils express other cytokines associated to airway remodeling, such as heparin-binding epidermal growth factor (HB-EGF), nerve growth factor (NGF), TGF-α and above all the Th2 cytokines IL-4 and IL-13 [ 98 , 99 ].…”

Naujienos apie eozinofilą: jų potipiai ir poveikis kvėpavimo takų nervų sistemai

“…EoP -eozinofilų progenitorinės ląstelės; hEOS -sumažėjusio tankio eozinofilai; HSPC -hematopoetinės ir progenitorinės ląstelės; IL -interleukinas; CD -diferenciacijos klasteris; nEOS -įprasto tankio eozinofilai. Pritaikyta remiantis [15]; © Licensee MDPI, Basel, Switzerland. kurie galutinai susiformuoja veikiami vietinės plaučių mikroaplinkos [18] (4 pav.).…”

“…Plaučių srities nulemtas eozinofilų plastiškumas EPX -eozinofilų neurotoksinas; GM-CSF -granulocitų-makrofagų augimo veiksnys; ICAM-1 -tarpląstelinė adhezijos molekulė 1; IFN-γ -interferonas γ; IL -interleukinas; ILC2 -antro tipo įgimtos limfoidinės ląstelės; MBP -didysis bazinis baltymas; NGF -nervų augimo veiksnys; Th2 -antro tipo T limfocitai pagalbininkai; TGF -transformuojantis augimo veiksnys. Pritaikyta remiantis[15]; © Licensee MDPI, Basel, Switzerland. IL-5 & IL-13 IL-4, IL-13, MBP, TGF-α, TGF-β, HB-EGF,…”