{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:16:05Z","timestamp":1792451765560,"version":"4.5.0"},"reference-count":114,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    conventional T cells (Tconvs) mediate adaptive immune responses, whereas regulatory T cells (Tregs) suppress those responses to safeguard the body from autoimmunity and inflammatory diseases. The opposing activities of Tconvs and Tregs depend on the stage of the immune response and their environment, with an orchestrating role for cytokine- and costimulatory receptors. Nutrient availability also impacts T-cell functionality\n                    <jats:italic>via<\/jats:italic>\n                    metabolic and biosynthetic processes that are largely unexplored. Many data argue that costimulation by Tumor Necrosis Factor Receptor 2 (TNFR2) favors support of Treg over Tconv responses and therefore TNFR2 is a key clinical target. Here, we review the pertinent literature on this topic and highlight the newly identified role of TNFR2 as a metabolic regulator for thymus-derived (t)Tregs. We present novel transcriptomic and metabolomic data that show the differential impact of TNFR2 on Tconv and tTreg gene expression and reveal distinct metabolic impact on both cell types.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.881166","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T06:16:58Z","timestamp":1656569818000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["TNFR2 Costimulation Differentially Impacts Regulatory and Conventional CD4+ T-Cell Metabolism"],"prefix":"10.3389","volume":"13","author":[{"given":"Mark","family":"Mensink","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Ngoc Minh","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther A.","family":"Zaal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Schrama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia R.","family":"Berkers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannie","family":"Borst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander","family":"de Kivit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.25.022106.141623","article-title":"Regulatory T Cells: Mechanisms of Differentiation and Function","volume":"30","author":"Josefowicz","year":"2012","journal-title":"Annu Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042718-041717","article-title":"Regulatory T Cells and Human Disease","volume":"38","author":"Sakaguchi","year":"2020","journal-title":"Annu Rev Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nri3605","article-title":"Homeostatic Control of Regulatory T Cell Diversity","volume":"14","author":"Liston","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/s41577-021-00519-w","article-title":"Tissue Regulatory T Cells: Regulatory Chameleons","volume":"21","author":"Munoz-Rojas","year":"2021","journal-title":"Rev Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0120-4","article-title":"Regulatory T Cells in Autoimmune Disease","volume":"19","author":"Dominguez-Villar","year":"2018","journal-title":"Nat Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/nyas.13011","article-title":"From IPEX Syndrome to FOXP3 Mutation: A Lesson on Immune Dysregulation","volume":"1417","author":"Bacchetta","year":"2018","journal-title":"Ann N Y Acad Sci"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cancerbio-030419-033428","article-title":"Regulatory T Cells in Cancer","volume":"4","author":"Plitas","year":"2020","journal-title":"Annu Rev Canc Biol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.jaut.2018.08.007","article-title":"A Comprehensive Review on the Role of Co-Signaling Receptors and Treg Homeostasis in Autoimmunity and Tumor Immunity","volume":"95","author":"Kumar","year":"2018","journal-title":"J Autoimmun"},{"key":"B9","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/s41577-019-0203-y","article-title":"Metabolic Coordination of T Cell Quiescence and Activation","volume":"20","author":"Chapman","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151159","article-title":"T Cell Metabolism Drives Immunity","volume":"212","author":"Buck","year":"2015","journal-title":"J Exp Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1016\/j.immuni.2018.04.008","article-title":"Proteomic Analyses of Human Regulatory T Cells Reveal Adaptations in Signaling Pathways That Protect Cellular Identity","volume":"48","author":"Cuadrado","year":"2018","journal-title":"Immunity"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.05.042","article-title":"FOXP3 Controls Regulatory T Cell Function Through Cooperation With NFAT","volume":"126","author":"Wu","year":"2006","journal-title":"Cell"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202659","article-title":"TNFR2 Is Critical for the Stabilization of the CD4+Foxp3+ Regulatory T. 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