IL‐1β promotes IL‐17A production of ILC3s to aggravate neutrophilic airway inflammation in mice

Yang, Dan; Li, Yi’na; Liu, Ting; Yang, Ling; He, Lixiu; Huang, Tao; Zhang, Lanlan; Luo, Jian; Liu, Chuntao

doi:10.1111/imm.13644

Cited by 4 publications

(1 citation statement)

References 104 publications

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“…Following skin injury, apoptotic neutrophils can initiate tissue repair via the release of lysophosphatidylserine (LysoPS), a direct stimulator of G protein-coupled receptor 34 (GPR34)-expressing ILC3s [55]. In mouse models of airway inflammation, elevated IL-1β levels promote the proliferation of IL-17 and CXCL1-producing ILC3s to recruit neutrophils to the lungs [56]. Elevated levels of IL-1β are linked to a variety of skin pathologies such as psoriasis, acne vulgaris, and cutaneous lupus erythematosus.…”

Section: Neutrophilsmentioning

confidence: 99%

Understanding Type 3 Innate Lymphoid Cells and Crosstalk with the Microbiota: A Skin Connection

To,

Oparaugo,

Kheshvadjian

et al. 2024

IJMS

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Innate lymphoid cells (ILCs) are a diverse population of lymphocytes classified into natural killer (NK) cells, ILC1s, ILC2s, ILC3s, and ILCregs, broadly following the cytokine secretion and transcription factor profiles of classical T cell subsets. Nonetheless, the ILC lineage does not have rearranged antigen-specific receptors and possesses distinct characteristics. ILCs are found in barrier tissues such as the skin, lungs, and intestines, where they play a role between acquired immune cells and myeloid cells. Within the skin, ILCs are activated by the microbiota and, in turn, may influence the microbiome composition and modulate immune function through cytokine secretion or direct cellular interactions. In particular, ILC3s provide epithelial protection against extracellular bacteria. However, the mechanism by which these cells modulate skin health and homeostasis in response to microbiome changes is unclear. To better understand how ILC3s function against microbiota perturbations in the skin, we propose a role for these cells in response to Cutibacterium acnes, a predominant commensal bacterium linked to the inflammatory skin condition, acne vulgaris. In this article, we review current evidence describing the role of ILC3s in the skin and suggest functional roles by drawing parallels with ILC3s from other organs. We emphasize the limited understanding and knowledge gaps of ILC3s in the skin and discuss the potential impact of ILC3-microbiota crosstalk in select skin diseases. Exploring the dialogue between the microbiota and ILC3s may lead to novel strategies to ameliorate skin immunity.

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Section: Neutrophilsmentioning

confidence: 99%

Understanding Type 3 Innate Lymphoid Cells and Crosstalk with the Microbiota: A Skin Connection

To,

Oparaugo,

Kheshvadjian

et al. 2024

IJMS

View full text Add to dashboard Cite

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Endotypes of severe neutrophilic and eosinophilic asthma from multi‐omics integration of U‐BIOPRED sputum samples

Kermani,

Li,

Versi

et al. 2024

Clinical & Translational Med

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BackgroundClustering approaches using single omics platforms are increasingly used to characterise molecular phenotypes of eosinophilic and neutrophilic asthma. Effective integration of multi‐omics platforms should lead towards greater refinement of asthma endotypes across molecular dimensions and indicate key targets for intervention or biomarker development.ObjectivesTo determine whether multi‐omics integration of sputum leads to improved granularity of the molecular classification of severe asthma.MethodsWe analyzed six ‐omics data blocks–microarray transcriptomics, gene set variation analysis of microarray transcriptomics, SomaSCAN proteomics assay, shotgun proteomics, 16S microbiome sequencing, and shotgun metagenomic sequencing–from induced sputum samples of 57 severe asthma patients, 15 mild‐moderate asthma patients, and 13 healthy volunteers in the U‐BIOPRED European cohort. We used Monti consensus clustering algorithm for aggregation of clustering results and Similarity Network Fusion to integrate the 6 multi‐omics datasets of the 72 asthmatics.ResultsFive stable omics‐associated clusters were identified (OACs). OAC1 had the best lung function with the least number of severe asthmatics with sputum paucigranulocytic inflammation. OAC5 also had fewer severe asthma patients but the highest incidence of atopy and allergic rhinitis, with paucigranulocytic inflammation. OAC3 comprised only severe asthmatics with the highest sputum eosinophilia. OAC2 had the highest sputum neutrophilia followed by OAC4 with both clusters consisting of mostly severe asthma but with more ex/current smokers in OAC4. Compared to OAC4, there was higher incidence of nasal polyps, allergic rhinitis, and eczema in OAC2. OAC2 had microbial dysbiosis with abundant Moraxella catarrhalis and Haemophilus influenzae. OAC4 was associated with pathways linked to IL‐22 cytokine activation, with the prediction of therapeutic response to anti‐IL22 antibody therapy.ConclusionMulti‐omics analysis of sputum in asthma has defined with greater granularity the asthma endotypes linked to neutrophilic and eosinophilic inflammation. Modelling diverse types of high‐dimensional interactions will contribute to a more comprehensive understanding of complex endotypes.Key Points Unsupervised clustering on sputum multi‐omics of asthma subjects identified 3 out of 5 clusters with predominantly severe asthma. One severe asthma cluster was linked to type 2 inflammation and sputum eosinophilia while the other 2 clusters to sputum neutrophilia. One severe neutrophilic asthma cluster was linked to Moraxella catarrhalis and to a lesser extent Haemophilus influenzae while the second cluster to activation of IL‐22.

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Downregulation of otulin induces inflammasome activation in neutrophilic asthma

Quoc,

Kim,

Park

et al. 2024

Journal of Allergy and Clinical Immunology

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IL‐1β promotes IL‐17A production of ILC3s to aggravate neutrophilic airway inflammation in mice

Cited by 4 publications

References 104 publications

Understanding Type 3 Innate Lymphoid Cells and Crosstalk with the Microbiota: A Skin Connection

Understanding Type 3 Innate Lymphoid Cells and Crosstalk with the Microbiota: A Skin Connection

Endotypes of severe neutrophilic and eosinophilic asthma from multi‐omics integration of U‐BIOPRED sputum samples

Downregulation of otulin induces inflammasome activation in neutrophilic asthma

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