Hydrogen Sulfide Promotes Tet1- and Tet2-mediated Foxp3 Demethylation to Drive Regulatory T Cell Differentiation and Maintain Immune Homeostasis

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dc.contributor.authorYang, Ruili
dc.contributor.authorQu, Cunye
dc.contributor.authorZhou, Yu
dc.contributor.authorKonkel, Joanne
dc.contributor.authorShi, Shihong
dc.contributor.authorLiu, Yi
dc.contributor.authorChen, Chider
dc.contributor.authorLiu, Shiyu
dc.contributor.authorLiu, Dawei
dc.contributor.authorChen, Yibu
dc.contributor.authorZandi, Ebrahim
dc.contributor.authorChen, Wanjun
dc.contributor.authorZhou, Yanheng
dc.contributor.authorShi, Songtao
dc.date2023-05-18T00:26:18.000
dc.date.accessioned2023-05-22T13:13:08Z
dc.date.available2023-05-22T13:13:08Z
dc.date.issued2015-08-18
dc.date.submitted2021-03-03T11:13:53-08:00
dc.description.abstractRegulatory T (Treg) cells are essential for maintenance of immune homeostasis. Here we found that hydrogen sulfide (H2S) was required for Foxp3+ Treg cell differentiation and function, and that H2S deficiency led to systemic autoimmune disease. H2S maintained expression of methylcytosine dioxygenases Tet1 and Tet2 by sulfhydrating nuclear transcription factor Y subunit beta (NFYB) to facilitate its binding to Tet1 and Tet2 promoters. Transforming growth factor-β (TGF-β)-activated Smad3 and interleukin-2 (IL-2)-activated Stat5 facilitated Tet1 and Tet2 binding to Foxp3. Tet1 and Tet2 catalyzed conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in Foxp3 to establish a Treg cell-specific hypomethylation pattern and stable Foxp3 expression. Consequently, Tet1 and Tet2 deletion led to Foxp3 hypermethylation, impaired Treg cell differentiation and function, and autoimmune disease. Thus, H2S promotes Tet1 and Tet2 expression, which are recruited to Foxp3 by TGF-β and IL-2 signaling to maintain Foxp3 demethylation and Treg cell-associated immune homeostasis.
dc.identifier.urihttps://repository.upenn.edu/handle/20.500.14332/8880
dc.legacy.articleid1267
dc.legacy.fields10.1016/j.immuni.2015.07.017
dc.legacy.fulltexturlhttps://repository.upenn.edu/cgi/viewcontent.cgi?article=1267&context=dental_papers&unstamped=1
dc.rights<p>© <2015>. This manuscript version is made available under the CC-BY-NC-ND 4.0 license <a href="http://creativecommons.org/licenses/by-nc-nd/4.0/">http://creativecommons.org/licenses/by-nc-nd/4.0/</a></p>
dc.source.beginpage251
dc.source.endpage263
dc.source.issue170
dc.source.issue2
dc.source.journalDepartmental Papers (Dental)
dc.source.journaltitleImmunity
dc.source.peerreviewedtrue
dc.source.statuspublished
dc.source.volume43
dc.subject.otherHydrogen Sulfide
dc.subject.otherregulatory T cells
dc.subject.otherten eleven translocation methylcytosine dioxygenases 1 and 2
dc.subject.otherdemethylation
dc.subject.other5-methylcytosine
dc.subject.othersulfhydration
dc.subject.otherDentistry
dc.titleHydrogen Sulfide Promotes Tet1- and Tet2-mediated Foxp3 Demethylation to Drive Regulatory T Cell Differentiation and Maintain Immune Homeostasis
dc.typeArticle
digcom.contributor.authorYang, Ruili
digcom.contributor.authorQu, Cunye
digcom.contributor.authorZhou, Yu
digcom.contributor.authorKonkel, Joanne
digcom.contributor.authorShi, Shihong
digcom.contributor.authorLiu, Yi
digcom.contributor.authorChen, Chider
digcom.contributor.authorLiu, Shiyu
digcom.contributor.authorLiu, Dawei
digcom.contributor.authorChen, Yibu
digcom.contributor.authorZandi, Ebrahim
digcom.contributor.authorChen, Wanjun
digcom.contributor.authorZhou, Yanheng
digcom.contributor.authorShi, Songtao
digcom.identifierdental_papers/170
digcom.identifier.contextkey21926119
digcom.identifier.submissionpathdental_papers/170
digcom.typearticle
dspace.entity.typePublication
upenn.schoolDepartmentCenterDepartmental Papers (Dental)
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