2014
DOI: 10.4049/jimmunol.1400614
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TLR2-Dependent Activation of β-Catenin Pathway in Dendritic Cells Induces Regulatory Responses and Attenuates Autoimmune Inflammation

Abstract: Dendritic cells (DCs) sense microbes via multiple innate receptors. Signals from different innate receptors are coordinated and integrated by DCs to generate specific innate and adaptive immune responses against pathogens. Previously, we have shown that two pathogen recognition receptors, TLR2 and dectin-1 that recognize the same microbial stimulus (zymosan) on DCs, induce mutually antagonistic regulatory or inflammatory responses, respectively. How diametric signals from these two receptors are coordinated in… Show more

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Cited by 68 publications
(93 citation statements)
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References 68 publications
(109 reference statements)
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“…In the present studies, we postulated that TLR tolerance could explain the TLR2 paradox in EAE as well as offer a potential mechanism for microbiome-mediated immune regulation. Our study differs from the polysaccharide A and zymosan studies (11)(12)(13)(14) in that we show TLR tolerance induction using a very low dose of a canonical TLR2 ligand and the microbiomederived TLR ligand known to access human serum, L654, attenuate EAE. Additionally, our study differs in our sole use of adoptive transfer EAE and in the effector and regulatory alterations we found associated with TLR tolerance-induced disease attenuation.…”
Section: Discussionmentioning
confidence: 72%
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“…In the present studies, we postulated that TLR tolerance could explain the TLR2 paradox in EAE as well as offer a potential mechanism for microbiome-mediated immune regulation. Our study differs from the polysaccharide A and zymosan studies (11)(12)(13)(14) in that we show TLR tolerance induction using a very low dose of a canonical TLR2 ligand and the microbiomederived TLR ligand known to access human serum, L654, attenuate EAE. Additionally, our study differs in our sole use of adoptive transfer EAE and in the effector and regulatory alterations we found associated with TLR tolerance-induced disease attenuation.…”
Section: Discussionmentioning
confidence: 72%
“…The TLR2 ligands, polysaccharide A and zymosan, when administered to mice during EAE (in the range of ∼100 mg per day), significantly reduced disease severity via induction of various subsets of Tregs (11)(12)(13)(14). In the present studies, we postulated that TLR tolerance could explain the TLR2 paradox in EAE as well as offer a potential mechanism for microbiome-mediated immune regulation.…”
Section: Discussionmentioning
confidence: 81%
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“…Todavia, não se pode ignorar que as DCs têm, também, outro papel essencial na manutenção do equilíbrio imune no organismo -a indução e manutenção da tolerância imunológica (CASTELLANO et al, 2004;MANOHARAN et al, 2014;NUSSEZWEIG, 2002;STEINMAN, 2003). Embora chamadas de "imaturas" quando não ativadas pelo desequilíbrio homeostático no tecido, as DCs, neste estado, são muito importantes para apresentar ao sistema imune antígenos presentes nos tecidos sadios, de maneira a evitar que se desencadeiem respostas destrutivas contra os mesmos (IDOYAGA et al, 2013;NUSSENZWEIG, 2002;STEINMAN, 2003), mantendo, portanto, a homeostasia tecidual.…”
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