ILC3 deficiency and generalized ILC abnormalities in DOCK8-deficient patients

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dc.authoridAyşenur Kaya / 0000-0002-8183-0190en_US
dc.authorscopusidAyşenur Kaya / 55544555800
dc.authorwosidAyşenur Kaya / AAO-7577-2020
dc.contributor.authorEken, Ahmet
dc.contributor.authorCansever, Murat
dc.contributor.authorOkuş, Fatma Zehra
dc.contributor.authorErdem, Şerife
dc.contributor.authorNain, Ercan
dc.contributor.authorAzizoğlu, Zehra Büşra
dc.contributor.authorHaliloğlu, Yeşim
dc.contributor.authorKarakukcu, Musa
dc.contributor.authorÖzcan, Alper
dc.contributor.authorDevecioğlu, Ömer
dc.contributor.authorAksu, Güzide
dc.contributor.authorArıkan Ayyıldız, Zeynep
dc.contributor.authorTopal, Erdem
dc.contributor.authorKarakoç Aydıner, Elif
dc.contributor.authorKıykım, Ayça
dc.contributor.authorMetin, Ayşe
dc.contributor.authorErol Çipe, Funda
dc.contributor.authorKaya, Ayşenur
dc.contributor.authorArtaç, Hasibe
dc.contributor.authorReisli, İsmail
dc.contributor.authorGüner, Şükrü N.
dc.contributor.authorUygun, Vedat
dc.contributor.authorTezcan Karasu, Gülsün
dc.contributor.authorDönmez Altuntaş, Hamiyet
dc.contributor.authorCanatan, Halit
dc.contributor.authorOukka, Mohamed
dc.contributor.authorÖzen, Ahmet
dc.contributor.authorChatila, Talal A.
dc.contributor.authorKeleş, Sevgi
dc.contributor.authorBarış, Safa
dc.contributor.authorÜnal, Ekrem
dc.contributor.authorPatıroğlu, Türkan
dc.date.accessioned2020-08-30T20:06:13Z
dc.date.available2020-08-30T20:06:13Z
dc.date.issued2020
dc.departmentİstinye Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümüen_US
dc.description.abstractBackgroundDedicator of cytokinesis 8 (DOCK8) deficiency is the main cause of the autosomal recessive hyper-IgE syndrome (HIES). We previously reported the selective loss of group 3 innate lymphoid cell (ILC) number and function in a Dock8-deficient mouse model. In this study, we sought to test whether DOCK8 is required for the function and maintenance of ILC subsets in humans. MethodsPeripheral blood ILC1-3 subsets of 16 DOCK8-deficient patients recruited at the pretransplant stage, and seven patients with autosomal dominant (AD) HIES due to STAT3 mutations, were compared with those of healthy controls or post-transplant DOCK8-deficient patients (n = 12) by flow cytometry and real-time qPCR. Sorted total ILCs from DOCK8- or STAT3-mutant patients and healthy controls were assayed for survival, apoptosis, proliferation, and activation by IL-7, IL-23, and IL-12 by cell culture, flow cytometry, and phospho-flow assays. ResultsDOCK8-deficient but not STAT3-mutant patients exhibited a profound depletion of ILC3s, and to a lesser extent ILC2s, in their peripheral blood. DOCK8-deficient ILC1-3 subsets had defective proliferation, expressed lower levels of IL-7R, responded less to IL-7, IL-12, or IL-23 cytokines, and were more prone to apoptosis compared with those of healthy controls. ConclusionDOCK8 regulates human ILC3 expansion and survival, and more globally ILC cytokine signaling and proliferation. DOCK8 deficiency leads to loss of ILC3 from peripheral blood. ILC3 deficiency may contribute to the susceptibility of DOCK8-deficient patients to infections.en_US
dc.description.sponsorshipNIAID NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R01 AI128976, R01 AI085090]en_US
dc.identifier.citationEken, A., Cansever, M., Okus, F. Z., Erdem, S., Nain, E., Azizoglu, Z. B., ... & Aksu, G. (2020). ILC3 deficiency and generalized ILC abnormalities in DOCK8‐deficient patients. Allergy, 75(4), 921-932.en_US
dc.identifier.doi10.1111/all.14081en_US
dc.identifier.endpage933en_US
dc.identifier.issn0105-4538en_US
dc.identifier.issn1398-9995en_US
dc.identifier.issue4en_US
dc.identifier.pmid31596517en_US
dc.identifier.scopus2-s2.0-85074777767en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage921en_US
dc.identifier.urihttps://doi.org/10.1111/all.14081
dc.identifier.urihttps://hdl.handle.net/20.500.12713/424
dc.identifier.volume75en_US
dc.identifier.wosWOS:000529134100017en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorKaya, Ayşenuren_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofAllergyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectDock8en_US
dc.subjectHyper-Ige Syndrome (Hies)en_US
dc.subjectIlcen_US
dc.subjectIlc3en_US
dc.subjectStat3en_US
dc.titleILC3 deficiency and generalized ILC abnormalities in DOCK8-deficient patientsen_US
dc.typeArticleen_US

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