{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T06:02:41Z","timestamp":1784872961525,"version":"3.55.0"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008672","name":"Wilhelm Sander-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Persistent antigenic stimulation leads to the dysfunction of CD8\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic T cells. These \u201cexhausted\u201d T\n                    <jats:sub>EX<\/jats:sub>\n                    cells exhibit reduced proliferative capacity, impaired effector function, and increased expression of co-inhibitory receptors. Chronic antigen receptor stimulation induces the expression of NFATc1\/\u03b1A, a short isoform of NFATc1 that promotes T\n                    <jats:sub>EX<\/jats:sub>\n                    cell survival. The induction of NFATc1\/\u03b1A is accompanied by a significant decrease in NFATc2 expression. NFATc2 limits the expression of stemness-associated genes, such as\n                    <jats:italic>Tcf7<\/jats:italic>\n                    ,\n                    <jats:italic>Sell<\/jats:italic>\n                    , and\n                    <jats:italic>Id3.<\/jats:italic>\n                    It also supports the expression of\n                    <jats:italic>Prf1<\/jats:italic>\n                    ,\n                    <jats:italic>Gzmb<\/jats:italic>\n                    , and the T\n                    <jats:sub>EX<\/jats:sub>\n                    marker gene\n                    <jats:italic>Havcr2<\/jats:italic>\n                    . Therefore, ablation of NFATc2 mitigates functional exhaustion of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells during chronic viral infection and antitumor immunity. Our findings illustrate that NFATc1 promotes the survival of T\n                    <jats:sub>EX<\/jats:sub>\n                    cells, while NFATc2 promotes the terminal differentiation and dysfunction of exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. The data suggest a non-redundant interplay between NFATc1 and NFATc2, each playing a distinct role in controlling CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell exhaustion. These findings open novel avenues to enhance the efficacy of immune checkpoint and CAR T-cell therapies.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1869029","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:35:32Z","timestamp":1784871332000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Non-redundant functions of NFATc1 in survival and NFATc2 in generation of exhausted CD8+ T cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Salvador","family":"Sampere-Birlanga","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology, Institute of Pathology, Julius-Maximilians-University of W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Klein-Hessling","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Institute of Pathology, Julius-Maximilians-University of W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Campillo Prados","sequence":"additional","affiliation":[{"name":"W\u00fcrzburg Institute of Systems Immunology, Max Planck Research Group at the Julius-Maximilians University of W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anfei","family":"Huang","sequence":"additional","affiliation":[{"name":"W\u00fcrzburg Institute of Systems Immunology, Max Planck Research Group at the Julius-Maximilians University of W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"W\u00fcrzburg Institute of Systems Immunology, Max Planck Research Group at the Julius-Maximilians University of W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Rosenwald","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Julius-Maximilians University of W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Kastenm\u00fcller","sequence":"additional","affiliation":[{"name":"W\u00fcrzburg Institute of Systems Immunology, Max Planck Research Group at the Julius-Maximilians University of W\u00fcrzburg","place":["W\u00fcrzburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Serfling","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Institute of Pathology, Julius-Maximilians-University of W\u00fcrzburg","place":["W\u00fcrzburg, 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