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DC Field | Value | Language |
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dc.citation.number | 15 | - |
dc.citation.startPage | 3981 | - |
dc.citation.title | CELL | - |
dc.citation.volume | 184 | - |
dc.contributor.author | Wong, Harikesh S. | - |
dc.contributor.author | Park, Kyemyung | - |
dc.contributor.author | Gola, Anita | - |
dc.contributor.author | Baptista, Antonio P. | - |
dc.contributor.author | Miller, Christine H. | - |
dc.contributor.author | Deep, Deeksha | - |
dc.contributor.author | Lou, Meng | - |
dc.contributor.author | Boyd, Lisa F. | - |
dc.contributor.author | Rudensky, Alexander Y. | - |
dc.contributor.author | Savage, Peter A. | - |
dc.contributor.author | Altan-Bonnet, Gregoire | - |
dc.contributor.author | Tsang, John S. | - |
dc.contributor.author | Germain, Ronald N. | - |
dc.date.accessioned | 2023-12-21T15:37:48Z | - |
dc.date.available | 2023-12-21T15:37:48Z | - |
dc.date.created | 2022-07-06 | - |
dc.date.issued | 2021-07 | - |
dc.description.abstract | A fraction of mature T cells can be activated by peripheral self-antigens, potentially eliciting host autoimmunity. We investigated homeostatic control of self-activated T cells within unperturbed tissue environments by combining high-resolution multiplexed and volumetric imaging with computational modeling. In lymph nodes, self-activated T cells produced interleukin (IL)-2, which enhanced local regulatory T cell (Treg) proliferation and inhibitory functionality. The resulting micro-domains reciprocally constrained inputs required for damaging effector responses, including CD28 co-stimulation and IL-2 signaling, constituting a negative feedback circuit. Due to these local constraints, self-activated T cells underwent transient clonal expansion, followed by rapid death (``pruning''). Computational simulations and experimental manipulations revealed the feedback machinery's quantitative limits: modest reductions in Treg micro-domain density or functionality produced non-linear breakdowns in control, enabling self-activated T cells to subvert pruning. This fine-tuned, paracrine feedback process not only enforces immune homeostasis but also establishes a sharp boundary between autoimmune and host-protective T cell responses. | - |
dc.identifier.bibliographicCitation | CELL, v.184, no.15, pp.3981 | - |
dc.identifier.doi | 10.1101/825943 | - |
dc.identifier.issn | 0092-8674 | - |
dc.identifier.scopusid | 2-s2.0-85110723414 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/58901 | - |
dc.identifier.wosid | 000676120800013 | - |
dc.language | 영어 | - |
dc.publisher | Cell Press | - |
dc.title | A local regulatory T cell feedback circuit maintains immune homeostasis by pruning self-activated T cells | - |
dc.type | Article | - |
dc.description.isOpenAccess | FALSE | - |
dc.type.docType | Article | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordAuthor | apoptosis | - |
dc.subject.keywordAuthor | autoimmunity | - |
dc.subject.keywordAuthor | computational modeling | - |
dc.subject.keywordAuthor | CTLA-4 | - |
dc.subject.keywordAuthor | feedback control | - |
dc.subject.keywordAuthor | IL-2 | - |
dc.subject.keywordAuthor | IL-2Rα | - |
dc.subject.keywordAuthor | immune homeostasis | - |
dc.subject.keywordAuthor | quantitative tissue imaging | - |
dc.subject.keywordAuthor | regulatory T cells | - |
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