Attenzione: i dati modificati non sono ancora stati salvati. Per confermare inserimenti o cancellazioni di voci è necessario confermare con il tasto SALVA/INSERISCI in fondo alla pagina
IRIS
Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required. Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity. Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes. Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin. Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.
IL-17–high asthma with features of a psoriasis immunophenotype
Ostling J.;van Geest M.;Schofield J. P. R.;Jevnikar Z.;Wilson S.;Ward J.;Lutter R.;Shaw D. E.;Bakke P. S.;Caruso M.;Dahlen S. -E.;Fowler S. J.;Horvath I.;Krug N.;Montuschi P.;Sanak M.;Sandstrom T.;Sun K.;Pandis I.;Auffray C.;Sousa A. R.;Guo Y.;Adcock I. M.;Howarth P.;Chung K. F.;Bigler J.;Sterk P. J.;Skipp P. J.;Djukanovic R.;Vaarala O.;Ahmed H.;Bakke P.;Bansal A. T.;Baribaud F.;Bates S.;Bel E. H.;Bisgaard H.;Boedigheimer M. J.;Bonnelykke K.;Brandsma J.;Brinkman P.;Bucchioni E.;Burg D.;Bush A.;Chaiboonchoe A.;Chanez P.;Compton C. H.;Corfield J.;D'Amico A.;Dahlen S. E.;De Meulder B.;Djukanovic R.;Erpenbeck V. J.;Erzen D.;Fichtner K.;Fitch N.;Fleming L. J.;Formaggio E.;Frey U.;Gahlemann M.;Geiser T.;Hashimoto S.;Haughney J.;Hedlin G.;Hekking P. W.;Higenbottam T.;Hohlfeld J. M.;Holweg C.;James A. J.;Knowles R.;Knox A. J.;Lefaudeux D.;Loza M. J.;Manta A.;Masefield S.;Mazein A.;Meiser A.;Middelveld R. J. M.;Miralpeix M.;Mores N.;Murray C. S.;Musial J.;Myles D.;Pahus L.;Pavlidis S.;Powell P.;Pratico G.;Rao M. P. N.;Riley J.;Roberts A.;Roberts G.;Rowe A.;Seibold W.;Selby A.;Sigmund R.;Singer F.;Thornton B.;van Aalderen W. M.;Vestbo J.;Vissing N. H.;Wagener A. H.;Wagers S. S.;Weiszhart Z.;Wheelock C. E.;Wilson S. J.;Aliprantis A.;Allen D.;Alving K.;Badorrek P.;Balgoma D.;Ballereau S.;Barber C.;Batuwitage M. K.;Bautmans A.;Bedding A.;Behndig A. F.;Beleta J.;Berglind A.;Berton A.;Bochenek G.;Braun A.;Campagna D.;Carayannopoulos L.;Casaulta C.;Chaleckis R.;Dahlen B.;Davison I.;De Alba J.;De Lepeleire I.;Dekker T.;Delin I.;Dennison P.;Dijkhuis A.;Dodson P.;Draper A.;Dyson K.;Edwards J.;El Hadjam L.;Emma R.;Ericsson M.;Faulenbach C.;Flood B.;Galffy G.;Gallart H.;Garissi D.;Gent J.;Gerhardsson de Verdier M.;Gibeon D.;Gomez C.;Gove K.;Gozzard N.;Guillmant-Farry E.;Henriksson E.;Hewitt L.;Hoda U.;Hu R.;Hu S.;Hu X.;Jeyasingham E.;Johnson K.;Jullian N.;Kamphuis J.;Kennington E. J.;Kerry D.;Kerry G.;Kluglich M.;Knobel H.;Kolmert J.;Konradsen J. R.;Kots M.;Kretsos K.;Krueger L.;Kuo S.;Kupczyk M.;Lambrecht B.;Lantz A. -S.;Larminie C.;Larsson L. X.;Latzin P.;Lazarinis N.;Lemonnier N.;Lone-Latif S.;Lowe L. A.;Marouzet L.;Martin J.;Mathon C.;McEvoy L.;Meah S.;Menzies-Gow A.;Metcalf L.;Mikus M.;Monk P.;Naz S.;Nething K.;Nicholas B.;Nihlen U.;Nilsson P.;Niven R.;Nordlund B.;Nsubuga S.;Pacino A.;Palkonen S.;Pellet J.;Pennazza G.;Petren A.;Pink S.;Pison C.;Postle A.;Rahman-Amin M.;Ravanetti L.;Ray E.;Reinke S.;Reynolds L.;Riemann K.;Robberechts M.;Rocha J. P.;Rossios C.;Russell K.;Rutgers M.;Santini G.;Santoninco M.;Saqi M.;Schoelch C.;Scott S.;Sehgal N.;Sjodin M.;Smids B.;Smith C.;Smith J.;Smith K. M.;Soderman P.;Sogbessan A.;Spycher F.;Staykova D.;Stephan S.;Stokholm J.;Strandberg K.;Sunther M.;Szentkereszty M.;Tamasi L.;Tariq K.;Thorngren J. -O.;Thorsen J.;Valente S.;van de Pol M.;van Drunen C. M.;Van Eyll J.;Versnel J.;Vink A.;von Garnier C.;Vyas A.;Wald F.;Walker S.;Wetzel K.;Wiegman C.;Williams S.;Yang X.;Yeyasingham E.;Amgen W. Y.;Zetterquist W.;Zolkipli Z.;Zwinderman A. H.
2019-01-01
Abstract
Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required. Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity. Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes. Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin. Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11387/191145
Citazioni
ND
94
ND
social impact
Conferma cancellazione
Sei sicuro che questo prodotto debba essere cancellato?
simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.
