{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:23:11Z","timestamp":1792718591324,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,29]],"date-time":"2023-01-29T00:00:00Z","timestamp":1674950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Korean government","doi-asserted-by":"publisher","award":["NRF-2017R1A2B3008621"],"award-info":[{"award-number":["NRF-2017R1A2B3008621"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korean government","doi-asserted-by":"publisher","award":["2021K2A9A2A06048161"],"award-info":[{"award-number":["2021K2A9A2A06048161"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korean government","doi-asserted-by":"publisher","award":["2022R1A2B5B03001840"],"award-info":[{"award-number":["2022R1A2B5B03001840"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korean government","doi-asserted-by":"publisher","award":["2022R1A4A5032688"],"award-info":[{"award-number":["2022R1A4A5032688"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korean government","doi-asserted-by":"publisher","award":["2020R1A6A3A13074208"],"award-info":[{"award-number":["2020R1A6A3A13074208"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Regulatory T (Treg) cells play an important role in immune homeostasis by inhibiting cells within the innate and adaptive immune systems; therefore, the stability and immunosuppressive function of Treg cells need to be maintained. In this study, we found that the expression of insulin receptor substrate 1 (IRS1) by Treg cells was lower than that by conventional CD4 T cells. IRS1-overexpressing Treg cells showed the downregulated expression of FOXP3, as well as Treg signature markers CD25 and CTLA4. IRS1-overexpressing Treg cells also showed diminished immunosuppressive functions in an in vitro suppression assay. Moreover, IRS1-overexpressing Treg cells were unable to suppress the pathogenic effects of conventional T cells in a transfer-induced colitis model. IRS1 activated the mTORC1 signaling pathway, a negative regulator of Treg cells. Moreover, IRS1 destabilized Treg cells by upregulating the expression of IFN-\u03b3 and Glut1. Thus, IRS1 acts as a negative regulator of Treg cells by downregulating the expression of FOXP3 and disrupting stability.<\/jats:p>","DOI":"10.3390\/ijms24032551","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T04:58:25Z","timestamp":1675054705000},"page":"2551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Insulin Receptor Substrate 1 Signaling Inhibits Foxp3 Expression and Suppressive Functions in Treg Cells through the mTORC1 Pathway"],"prefix":"10.3390","volume":"24","author":[{"given":"Woo Ho","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga Eul","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Jin","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeong Su","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6412-9482","authenticated-orcid":false,"given":"Gap Ryol","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1146\/annurev-immunol-030409-101212","article-title":"Differentiation of effector CD4 T cell populations (*)","volume":"28","author":"Zhu","year":"2010","journal-title":"Annu. 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