Severe COVID-19 patients exhibit an ILC2 NKG2D+ population in their impaired ILC compartment

Gomez-Cadena, Alejandra; Spehner, Laurie; Kroemer, Marie; Khelil, Myriam Ben; Bouiller, Kévin; Verdeil, Grégory; Trabanelli, Sara; Borg, Christophe; Loyon, Romain; Jandus, Camilla

doi:10.1038/s41423-020-00596-2

Cited by 45 publications

(67 citation statements)

References 10 publications

(7 reference statements)

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“…The risk for severe illness with SARS-CoV-2 increases with age, with older adults (>65 years) having five times more probability of developing severe COVID-19 disease (68). It has been reported that there is an increased level of systemic IL-33 in the serum and plasma of severe COVID-19 patients, together with an increased number of circulating ILC2 (69). Furthermore, it has been reported that increased levels of IL-18, IL-13, and IL-6 were increased along with accumulation of ILC2 during COVID-19 that could be linked with the severity of the diseases.…”

Section: Sars-cov-2 Induced Ilc2mentioning

confidence: 99%

Role of ILC2 in Viral-Induced Lung Pathogenesis

et al. 2021

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Innate lymphoid type-2 cells (ILC2) are a population of innate cells of lymphoid origin that are known to drive strong Type 2 immunity. ILC2 play a key role in lung homeostasis, repair/remodeling of lung structures following injury, and initiation of inflammation as well as more complex roles during the immune response, including the transition from innate to adaptive immunity. Remarkably, dysregulation of this single population has been linked with chronic lung pathologies, including asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrotic diseases (IPF). Furthermore, ILC2 have been shown to increase following early-life respiratory viral infections, such as respiratory syncytial virus (RSV) and rhinovirus (RV), that may lead to long-term alterations of the lung environment. The detrimental roles of increased ILC2 following these infections may include pathogenic chronic inflammation and/or alterations of the structural, repair, and even developmental processes of the lung. Respiratory viral infections in older adults and patients with established chronic pulmonary diseases often lead to exacerbated responses, likely due to previous exposures that leave the lung in a dysregulated functional and structural state. This review will focus on the role of ILC2 during respiratory viral exposures and their effects on the induction and regulation of lung pathogenesis. We aim to provide insight into ILC2-driven mechanisms that may enhance lung-associated diseases throughout life. Understanding these mechanisms will help identify better treatment options to limit not only viral infection severity but also protect against the development and/or exacerbation of other lung pathologies linked to severe respiratory viral infections.

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Section: Sars-cov-2 Induced Ilc2mentioning

confidence: 99%

Role of ILC2 in Viral-Induced Lung Pathogenesis

et al. 2021

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“… 1 Recent observations have revealed that serum IL-33 is upregulated in elderly patients with COVID-19 and associated with adverse outcomes. 2 , 3 The increased IL-33 levels in severe infection could result from epithelial damage caused by strong interactions between the airway epithelium and activated immune cells. SARS-CoV-2-derived papain-like protease (PLpro), a powerful inducer of IL-33 in epithelial cells, 4 may also trigger epithelium-derived IL-33 to initiate inflammatory responses in the lungs.…”

mentioning

confidence: 99%

“… 1 Compared with severe acute respiratory syndrome coronavirus (SAR-CoV), SAR-CoV-2 favors a cytokine storm composed of low levels of type 1 cytokines (IL-12p70 and IL-15) but high expression of Th2/9 cytokines (IL-4, IL-9, IL-10, IL-13 and TGF-β). 7 Elevated type 2 cytokine levels correlated with an increased number of ILC2s in COVID-19 patients 3 and may contribute to the differentiation of pathogenic γδ T cells (IFN-γ low GM-CSF high ). Therefore, an elevation in IL-33 in the lungs following SAR-CoV-2 infection might be the driving force of type 2 immune cytokines and account for respiratory immune dysregulation.…”

mentioning

confidence: 99%

IL-33 in COVID-19: friend or foe?

Liang

Sun

2021

Cell Mol Immunol

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“…Indeed, this treatment led to increased lung numbers of IL-5 + ILC2s and subsequent eosinophilia indicating that SARS-CoV2 could directly drive ILC2 responses in infected human lungs via PLpro. In the same study, flow cytometric analysis revealed a relative increase of ILC2 frequencies in the peripheral blood in mild to severe COVID-19 disease, while the pool of total ILCs was lower compared to healthy controls ( 71 ). Interestingly, within ILC2s, a subset expressing low levels of the receptor tyrosine kinase cKit was significantly expanded in patients with severe COVID-19 disease, possibly consistent with an accumulation of mature ILC2s.…”

Section: Ilc2s As Gatekeepers Of Lung Homeostasismentioning

confidence: 70%

“…Because the SARS-CoV2 genome encodes for the essential papain-like protease PLpro ( 70 ), Gomez-Cadena et al. administered this protein intranasally on five consecutive days to mice ( 71 ). Indeed, this treatment led to increased lung numbers of IL-5 + ILC2s and subsequent eosinophilia indicating that SARS-CoV2 could directly drive ILC2 responses in infected human lungs via PLpro.…”

Section: Ilc2s As Gatekeepers Of Lung Homeostasismentioning

confidence: 99%

Functional Contribution and Targeted Migration of Group-2 Innate Lymphoid Cells in Inflammatory Lung Diseases: Being at the Right Place at the Right Time

2021

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During the last decade, group-2 innate lymphoid cells (ILC2s) have been discovered and successfully established as crucial mediators of lung allergy, airway inflammation and fibrosis, thus affecting the pathogenesis and clinical course of many respiratory diseases, like for instance asthma, cystic fibrosis and chronic rhinosinusitis. As an important regulatory component in this context, the local pulmonary milieu at inflammatory tissue sites does not only determine the activation status of lung-infiltrating ILC2s, but also influences their motility and migratory behavior. In general, many data collected in recent murine and human studies argued against the former concept of a very strict tissue residency of innate lymphoid cells (ILCs) and instead pointed to a context-dependent homing capacity of peripheral blood ILC precursors and the inflammation-dependent capacity of specific ILC subsets for interorgan trafficking. In this review article, we provide a comprehensive overview of the so far described molecular mechanisms underlying the pulmonary migration of ILC2s and thereby the numeric regulation of local ILC2 pools at inflamed or fibrotic pulmonary tissue sites and discuss their potential to serve as innovative therapeutic targets in the treatment of inflammatory lung diseases.

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Severe COVID-19 patients exhibit an ILC2 NKG2D+ population in their impaired ILC compartment

Cited by 45 publications

References 10 publications

Role of ILC2 in Viral-Induced Lung Pathogenesis

Role of ILC2 in Viral-Induced Lung Pathogenesis

IL-33 in COVID-19: friend or foe?

Functional Contribution and Targeted Migration of Group-2 Innate Lymphoid Cells in Inflammatory Lung Diseases: Being at the Right Place at the Right Time

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