Identification of extracellular vesicle microRNA signatures specifically linked to inflammatory and metabolic mechanisms in obesity-associated low type-2 asthma.
asthma endotypes
asthma phenotypes
extracellular vesicles
microRNA clusters
obesity-associated asthma
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
revised:
26
05
2023
received:
03
04
2023
accepted:
05
06
2023
medline:
13
11
2023
pubmed:
24
7
2023
entrez:
24
7
2023
Statut:
ppublish
Résumé
Plasma extracellular vesicles (EVs) represent a vital source of molecular information about health and disease states. Due to their heterogenous cellular sources, EVs and their cargo may predict specific pathomechanisms behind disease phenotypes. Here we aimed to utilize EV microRNA (miRNA) signatures to gain new insights into underlying molecular mechanisms of obesity-associated low type-2 asthma. Obese low type-2 asthma (OA) and non-obese low type-2 asthma (NOA) patients were selected from an asthma cohort conjointly with healthy controls. Plasma EVs were isolated and characterised by nanoparticle tracking analysis. EV-associated small RNAs were extracted, sequenced and bioinformatically analysed. Based on EV miRNA expression profiles, a clear distinction between the three study groups could be established using a principal component analysis. Integrative pathway analysis of potential target genes of the differentially expressed miRNAs revealed inflammatory cytokines (e.g., interleukin-6, transforming growth factor-beta, interferons) and metabolic factors (e.g., insulin, leptin) signalling pathways to be specifically associated with OA. The miR-17-92 and miR-106a-363 clusters were significantly enriched only in OA. These miRNA clusters exhibited discrete bivariate correlations with several key laboratory (e.g., C-reactive protein) and lung function parameters. Plasma EV miRNA signatures mirrored blood-derived CD4 The identified plasma EV miRNA signatures and particularly the miR-17-92 and -106a-363 clusters were capable to disentangle specific mechanisms of the obesity-associated low type-2 asthma phenotype, which may serve as basis for stratified treatment development.
Substances chimiques
MicroRNAs
0
Cytokines
0
Interleukin-6
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2944-2958Subventions
Organisme : German Academic Exchange Service (DAAD)
Organisme : German Center for Lung Research (DZL)
Organisme : Hessen State Ministry for Higher Education, Research, Science and and the Arts
Informations de copyright
© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
Références
Mohan A, Agarwal S, Clauss M, Britt NS, Dhillon NK. Extracellular vesicles: novel communicators in lung diseases. Respir Res. 2020;21(1):175.
Alhamwe BA, Potaczek DP, Miethe S, et al. Extracellular vesicles and asthma-more than just a co-existence. Int J Mol Sci. 2021;22(9):4984.
Holcar M, Ferdin J, Sitar S, et al. Enrichment of plasma extracellular vesicles for reliable quantification of their size and concentration for biomarker discovery. Sci Rep. 2020;10(1):1-13.
Lim HC, Soneji S, Pálmason R, Lenhoff S, Laurell T, Scheding S. Development of acoustically isolated extracellular plasma vesicles for biomarker discovery in allogeneic hematopoietic stem cell transplantation. Biomark Res. 2021;9(1):6.
Potaczek DP, Miethe S, Schindler V, Alhamdan F, Garn H. Role of airway epithelial cells in the development of different asthma phenotypes. Cell Signal. 2020;69:109523.
Mori MA, Ludwig RG, Garcia-Martin R, Brandão BB, Kahn CR. Extracellular miRNAs: from biomarkers to mediators of physiology and disease. Cell Metab. 2019;30(4):656-673.
Bartel S, la Grutta S, Cilluffo G, et al. Human airway epithelial extracellular vesicle miRNA signature is altered upon asthma development. Allergy. 2020;75(2):346-356.
Eckhardt CM, Gambazza S, Bloomquist TR, et al. Extracellular vesicle-encapsulated microRNAs as novel biomarkers of lung health. Am J Respir Crit Care Med. 2023;207(1):50-59.
Mims JW. Asthma: definitions and pathophysiology. Int Forum Allergy Rhinol. 2015;5(S1):S2-S6.
Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012;18(5):716-725.
Akhter N, Begum K, Nahar P, et al. Risk factors for non-communicable diseases related to obesity among first- and second-generation Bangladeshi migrants living in north-east or south-East England. Int J Obes (Lond). 2021;45(7):1588-1598.
Miethe S, Guarino M, Alhamdan F, et al. Effects of obesity on asthma: Immunometabolic links. Pol Arch Intern Med. 2018;128(7-8):469-477.
Reddon H, Guéant JL, Meyre D. The importance of gene-environment interactions in human obesity. Clin Sci. 2016;130(18):1571-1597.
Potaczek DP, Harb H, Michel S, Alhamwe BA, Renz H, Tost J. Epigenetics and allergy: from basic mechanisms to clinical applications. Epigenomics. 2017;9(4):539-571.
Alashkar Alhamwe B, Alhamdan F, Ruhl A, Potaczek DP, Renz H. The role of epigenetics in allergy and asthma development. Curr Opin Allergy Clin Immunol. 2020;20(1):48-55.
Haldar P, Pavord ID, Shaw DE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med. 2012;178(3):218-224.
Moore WC, Meyers DA, Wenzel SE, et al. Identification of asthma phenotypes using cluster analysis in the severe asthma research program. Am J Respir Crit Care Med. 2012;181(4):315-323.
Reddel HK, Bacharier LB, Bateman ED, et al. Global initiative for asthma strategy 2021: executive summary and rationale for key changes. Eur Resp J. 2022;59(1):2102730.
Alhamdan F, Marsh LM, Pedersen F, et al. Differential regulation of interferon signaling pathways in CD4+ T cells of the low type-2 obesity-associated asthma phenotype. Int J Mol Sci. 2021;22(18):10144.
Billing U, Jetka T, Nortmann L, et al. Robustness and information transfer within IL-6-induced JAK/STAT Signalling. Commun Biol. 2019;2(1):1-14.
Costa-Pereira AP. Regulation of IL-6-type cytokine responses by MAPKs. Biochem Soc Trans. 2014;42(1):59-62.
Kern F, Fehlmann T, Solomon J, et al. miEAA 2.0: integrating multi-species microRNA enrichment analysis and workflow management systems. Nucleic Acids Res. 2021;48(W1):W521-W528.
Kabekkodu SP, Shukla V, Varghese VK, d'Souza J, Chakrabarty S, Satyamoorthy K. Clustered miRNAs and their role in biological functions and diseases. Biol Rev. 2018;93(4):1955-1986.
Li J, Han X, Wan Y, et al. TAM 2.0: tool for MicroRNA set analysis. Nucleic Acids Res. 2018;46(W1):W180-W185.
Matson SM, Sundar IK. The promise of liquid biopsies: extracellular vesicle-microRNAs open the door to future study in lung disease. Am J Respir Crit Care Med. 2023;207(1):7-9.
Kuruvilla ME, Lee FEH, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2018;56(2):219-233.
Denti P, Wasmann RE, Francis J, et al. One dose does not fit all: revising the WHO paediatric dosing tool to include the non-linear effect of body size and maturation. Lancet Child Adolesc Health. 2022;6(1):9-10.
Garcia-Martin R, Wang G, Brandão BB, et al. MicroRNA sequence codes for small extracellular vesicle release and cellular retention. Nature. 2022;601(7893):446-451.
Jeppesen DK, Fenix AM, Franklin JL, et al. Reassessment of exosome composition. Cell. 2019;177(2):428-445.e18.
Montecalvo A, Larregina AT, Shufesky WJ, et al. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood. 2012;119(3):756-766.
Mendell JT. miRiad roles for the miR-17-92 cluster in development and disease. Cell. 2008;133(2):217-222.
Gagliardo R, Chanez P, Gjomarkaj M, et al. The role of transforming growth factor-β1 in airway inflammation of childhood asthma. Int J Immunopathol Pharmacol. 2013;26(3):725-738.
Stadler JT, Marsche G. Obesity-related changes in high-density lipoprotein metabolism and function. Int J Mol Sci. 2020;21(23):1-28.
Wang Q, Yan CL, Wang J, et al. miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130. Proc Natl Acad Sci U S A. 2008;105(8):2889-2894.
Zhang X, Liu J, Wu L, Hu X. Micrornas of the mir-17 ~ 9 family maintain adipose tissue macrophage homeostasis by sustaining il-10 expression. Elife. 2020;9:1-19.
Jiang S, Li C, Olive V, et al. Molecular dissection of the miR-17-92 cluster's critical dual roles in promoting Th1 responses and preventing inducible Treg differentiation. Blood. 2011;118(20):5487-5497.
Dölz M, Hasiuk M, Gagnon JD, et al. Forced expression of the non-coding RNA miR-17∼92 restores activation and function in CD28−deficient CD4+ T cells. iScience. 2022;25(11):105372.
Kang SG, Liu WH, Lu P, et al. MicroRNAs of the miR-17∼92 family are critical regulators of TFH differentiation. Nat Immunol. 2013;14(8):849-857.
Baumjohann D, Kageyama R, Clingan JM, et al. The microRNA cluster miR-17∼92 promotes TFH cell differentiation and represses subset-inappropriate gene expression. Nat Immunol. 2013;14(8):840-848.
Khan AA, Penny LA, Yuzefpolskiy Y, Sarkar S, Kalia V. MicroRNA-17∼92 regulates effector and memory CD8 T-cell fates by modulating proliferation in response to infections. Blood. 2013;121(22):4473-4483.
Kosaka A, Ohkuri T, Ikeura M, Kohanbash G, Okada H. Transgene-derived overexpression of miR-17-92 in CD8+ T-cells confers enhanced cytotoxic activity. Biochem Biophys Res Commun. 2015;458(3):549-554.
Montoya MM, Maul J, Singh PB, et al. A distinct inhibitory function for miR-18a in Th17 cell differentiation. J Immunol. 2017;199(2):559-569.
Schindler VEM, Alhamdan F, Preußer C, et al. Side-directed release of differential extracellular vesicle-associated microRNA profiles from bronchial epithelial cells of healthy and asthmatic subjects. Biomedicine. 2022;10(3):622.
Li H, Li T, Wang S, et al. MiR-17-5p and miR-106a are involved in the balance between osteogenic and adipogenic differentiation of adipose-derived mesenchymal stem cells. Stem Cell Res. 2013;10(3):313-324.
Kästle M, Bartel S, Geillinger-Kästle K, et al. microRNA cluster 106a~363 is involved in T helper 17 cell differentiation. Immunology. 2017;152(3):402-413.
Mathelier A, Carbone A. Large scale chromosomal mapping of human microRNA structural clusters. Nucleic Acids Res. 2013;41(8):4392-4408.
Jevnikar Z, Östling J, Ax E, et al. Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation. J Allergy Clin Immunol. 2019;143(2):577-590.
Richard AJ, Stephens JM. The role of JAK-STAT signaling in adipose tissue function. Biochim Biophys Acta Mol Basis Dis. 2014;1842(3):431-439.
Majoros A, Platanitis E, Kernbauer-Hölzl E, Rosebrock F, Müller M, Decker T. Canonical and non-canonical aspects of JAK-STAT signaling: lessons from interferons for cytokine responses. Front Immunol. 2017;8:29.
Rojas JM, Alejo A, Martín V, Sevilla N. Viral pathogen-induced mechanisms to antagonize mammalian interferon (IFN) signaling pathway. Cell Mol Life Sci. 2021;78(4):1423-1444.
Dixon AE, Que LG. Interplay between immune and airway smooth muscle cells in obese asthma. Am J Respir Crit Care Med. 2023;207(4):388-389.
Yon C, Thompson DA, Jude JA, Panettieri RA Jr, Rastogi D. Crosstalk between CD4+ T cells and airway smooth muscle in pediatric obesity-related asthma. Am J Respir Crit Care Med. 2023;207(4):461-474.