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Editorial
. 2020 Oct 15;202(8):1067-1069.
doi: 10.1164/rccm.202007-2658ED.

Activation of Group 2 Innate Lymphoid Cells via TL1A/DR3. A Solution to Corticosteroid Resistance?

Chrysanthi Skevaki  1 , Markus Weckmann  2
Affiliations
Editorial

Activation of Group 2 Innate Lymphoid Cells via TL1A/DR3. A Solution to Corticosteroid Resistance?

Chrysanthi Skevaki et al. Am J Respir Crit Care Med. .
No abstract available

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Figures

Figure 1.
Figure 1.
Innate lymphoid group 2 cell (ILC2) endotypes contribute to severe asthma phenotypes across all ages. (A) Severe asthma phenotypes (red circle) are clinically identified in cross-sectional analysis as a result of comparison to symptomatically milder phenotypes (blue/red or green/blue circles) or control subjects (green circle). These differences may then drive a deep phenotyping approach. (B) Severe phenotypes are analyzed by, for example, multiomics or hypothesis-specific tools (e.g., flow cytometry of DR3 [death receptor 3]-positive ILC2s as presented by Machida and colleagues in this issue of the Journal [3]), and a palette of several, possibly coexisting, endotypes emerges. Further characterization of the phenotypic characteristics of each endotype help to establish “ground truth” for asthma heterogeneity. Importantly, this is not limited to severe phenotypes alone but extends also to milder asthma and even asthma remission. (C) It is conceivable that these coexisting endotypes may have developed over time by endogenous and exogenous drivers, but little is known about the prerequisites for many of these endotypes and how they coexist. At young age, risk factors are associated with asthma pathogenesis; however, phenotypic expression is low (light purple vs., e.g., orange circle). During preschool age, first symptomatic episodes distinguish between children with an ever-increasing risk to be diagnosed with asthma at school age (dark orange circle) and those with, for example, intermittent wheeze (purple circle). At which point an ILC2-driven immune response becomes established or even dominates the asthmatic phenotype is not well understood. Moreover, features such as auto-antibodies against eosinophil peroxidase are not routinely tested, so early emergence of such a subendotype goes undetected. Longitudinal deep-phenotyping cohorts heavily rely on cross-sectional data (such as Machida and colleagues’) to trace the origins of these complex endotypes and help to provide other biomarkers, preventive measures, and early disease-modifying strategies.
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Comment on

References

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