{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Dillon S"],"funding":["NIDDK NIH HHS","NIAID NIH HHS"],"pagination":["916-28"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC1401484"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["116(4)"],"pubmed_abstract":["Emerging evidence suggests critical roles for APCs in suppressing immune responses. Here, we show that zymosan, a stimulus for TLR2 and dectin-1, regulates cytokine secretion in DCs and macrophages to induce immunological tolerance. First, zymosan induces DCs to secrete abundant IL-10 but little IL-6 and IL-12(p70). Induction of IL-10 is dependent on TLR2- and dectin-1-mediated activation of ERK MAPK via a mechanism independent of the activation protein 1 (AP-1) transcription factor c-Fos. Such DCs stimulate antigen-specific CD4+ T cells poorly due to IL-10 and the lack of IL-6. Second, zymosan induces F4-80+ macrophages in the splenic red pulp to secrete TGF-beta. Consistent with these effects on APCs, injection of zymosan plus OVA into mice results in OVA-specific T cells that secrete little or no Th1 or Th2 cytokines, but secrete robust levels of IL-10, and are unresponsive to challenge with OVA plus adjuvant. Finally, coinjection of zymosan with OVA plus LPS suppresses the response to OVA via a mechanism dependent on IL-10, TGF-beta, and lack of IL-6. Together, our data demonstrate that zymosan stimulates IL-10+ IL-12(p70)- IL-6low regulatory DCs and TGF-beta+ macrophages to induce immunological tolerance. These data suggest several targets for pharmacological modulation of immune responses in various clinical settings."],"journal":["The Journal of clinical investigation"],"pubmed_title":["Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance."],"pmcid":["PMC1401484"],"funding_grant_id":["R56 AI048638","R01 DK057665","R37 AI048638","R37 DK057665","AI057157","AI05726601","AI0564499","DK057665","U54 AI057157","R01 AI048638","AI048638"],"pubmed_authors":["Agrawal S","Pare J","Unutmaz D","Kasprowicz DJ","Pulendran B","Denning TL","Kellar K","Letterio J","Oswald-Richter K","van Dyke T","Dillon S","Banerjee K","Ziegler S"],"additional_accession":[]},"is_claimable":false,"name":"Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance.","description":"Emerging evidence suggests critical roles for APCs in suppressing immune responses. Here, we show that zymosan, a stimulus for TLR2 and dectin-1, regulates cytokine secretion in DCs and macrophages to induce immunological tolerance. First, zymosan induces DCs to secrete abundant IL-10 but little IL-6 and IL-12(p70). Induction of IL-10 is dependent on TLR2- and dectin-1-mediated activation of ERK MAPK via a mechanism independent of the activation protein 1 (AP-1) transcription factor c-Fos. Such DCs stimulate antigen-specific CD4+ T cells poorly due to IL-10 and the lack of IL-6. Second, zymosan induces F4-80+ macrophages in the splenic red pulp to secrete TGF-beta. Consistent with these effects on APCs, injection of zymosan plus OVA into mice results in OVA-specific T cells that secrete little or no Th1 or Th2 cytokines, but secrete robust levels of IL-10, and are unresponsive to challenge with OVA plus adjuvant. Finally, coinjection of zymosan with OVA plus LPS suppresses the response to OVA via a mechanism dependent on IL-10, TGF-beta, and lack of IL-6. Together, our data demonstrate that zymosan stimulates IL-10+ IL-12(p70)- IL-6low regulatory DCs and TGF-beta+ macrophages to induce immunological tolerance. These data suggest several targets for pharmacological modulation of immune responses in various clinical settings.","dates":{"release":"2006-01-01T00:00:00Z","publication":"2006 Apr","modification":"2024-11-13T17:01:56.715Z","creation":"2019-03-27T01:26:05Z"},"accession":"S-EPMC1401484","cross_references":{"pubmed":["16543948"],"doi":["10.1172/jci27203","10.1172/JCI27203"]}}