Autoimmune regulator (AIRE) contributes to Dectin-1-induced TNF-alpha production and complexes with caspase recruitment domain-containing protein 9 (CARD9), spleen tyrosine kinase (Syk), and Dectin-1

dc.creatorPedroza, Luis A.
dc.creatorKumar, Vipul
dc.creatorSanborn, Keri B.
dc.creatorMace, Emily M.
dc.creatorNiinikoski, Harri
dc.creatorNadeau, Kari
dc.creatorVasconcelos, Dewton de Moraes
dc.creatorPerez, Elena
dc.creatorJyonouchi, Soma
dc.creatorJyonouchi, Harumi
dc.creatorBanerjee, Pinaki P.
dc.creatorRuuskanen, Olli
dc.creatorCondino-Neto, Antonio
dc.creatorOrange, Jordan S.
dc.date2012
dc.date2013-09-19T18:06:28Z
dc.date2016-07-01T15:47:30Z
dc.date2013-09-19T18:06:28Z
dc.date2016-07-01T15:47:30Z
dc.date.accessioned2018-03-29T01:56:16Z
dc.date.available2018-03-29T01:56:16Z
dc.identifierJournal of Allergy and Clinical Immunology. Mosby-Elsevier, v.129, n.2, p.464-U287, 2012
dc.identifier0091-6749
dc.identifierWOS:000299951700026
dc.identifier10.1016/j.jaci.2011.08.027
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/2178
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/2178
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1309004
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionBackground: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome is a complex immunologic disease caused by mutation of the autoimmune regulator (AIRE) gene. Autoimmunity in patients with APECED syndrome has been shown to result from deficiency of AIRE function in transcriptional regulation of thymic peripheral tissue antigens, which leads to defective T-cell negative selection. Candidal susceptibility in patients with APECED syndrome is thought to result from aberrant adaptive immunity. Objective: To determine whether AIRE could function in anticandidal innate immune signaling, we investigated an extrathymic role for AIRE in the immune recognition of beta-glucan through the Dectin-1 pathway, which is required for defense against Candida species. Methods: Innate immune signaling through the Dectin-1 pathway was assessed in both PBMCs from patients with APECED syndrome and a monocytic cell line. Subcellular localization of AIRE was assessed by using confocal microscopy. Results: PBMCs from patients with APECED syndrome had reduced TNF-alpha responses after Dectin-1 ligation but in part used a Raf-1-mediated pathway to preserve function. In the THP-1 human monocytic cell line, reducing AIRE expression resulted in significantly decreased TNF-a release after Dectin-1 ligation. AIRE formed a transient complex with the known Dectin-1 pathway components phosphorylated spleen tyrosine kinase and caspase recruitment domain-containing protein 9 after receptor ligation and localized with Dectin-1 at the cell membrane. Conclusion: AIRE can participate in the Dectin-1 signaling pathway, indicating a novel extrathymic role for AIRE and a defect that likely contributes to fungal susceptibility in patients with APECED syndrome. (J Allergy Clin Immunol 2012;129:464-72.)
dc.description129
dc.description2
dc.description464
dc.descriptionU287
dc.descriptionChildren's Hospital of Philadelphia
dc.descriptionJeffrey Modell Diagnostic Center
dc.descriptionUniversity of Pennsylvania
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.languageeng
dc.publisherMosby-Elsevier
dc.publisherNew York
dc.relationJournal of Allergy and Clinical Immunology
dc.rightsfechado
dc.sourceWOS
dc.subjectPrimary immunodeficiency
dc.subjectinnate immunity
dc.subjectchronic mucocutaneous candidiasis
dc.subjectmonocytes
dc.subjectCHRONIC MUCOCUTANEOUS CANDIDIASIS
dc.subjectIMMUNOLOGICAL SYNAPSE
dc.subjectECTODERMAL DYSTROPHY
dc.subjectCYTOKINE PRODUCTION
dc.subjectFUNGAL-INFECTIONS
dc.subjectACTIVATION
dc.subjectGENE
dc.subjectRECOGNITION
dc.subjectINDUCTION
dc.subjectIMMUNITY
dc.titleAutoimmune regulator (AIRE) contributes to Dectin-1-induced TNF-alpha production and complexes with caspase recruitment domain-containing protein 9 (CARD9), spleen tyrosine kinase (Syk), and Dectin-1
dc.typeArtículos de revistas


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