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Calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) signaling is essential for this process, and the complexity of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels presents a potential therapeutic target for modulating the strength of TCR signaling and further differentiation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010mobilizing second messenger that triggers Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release through ryanodine receptor 1 (RYR1) in T cells. While the molecular and biophysical properties of NAADP\u2010induced Ca\n                    <jats:sup>2+<\/jats:sup>\n                    microdomains in T cells have been thoroughly investigated and the function of the NAADP\u2013HN1L\/JPT2\u2013RYR1 axis has been supported in T\u2010cell activation and proliferation, its role in intestinal inflammation in vivo remains to be elucidated. In this study, we generated a conditional knockout mouse with\n                    <jats:italic>Ryr1<\/jats:italic>\n                    deleted in \u03b1\u03b2 T cells to investigate the functional relevance of RYR1 signaling in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells.\n                    <jats:italic>Ryr1<\/jats:italic>\n                    deletion in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells decreased TCR\u2010induced Ca\n                    <jats:sup>2+<\/jats:sup>\n                    microdomain formation, reduced peak Ca\n                    <jats:sup>2+<\/jats:sup>\n                    amplitude, and delayed the initial velocity of global Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling in vitro. However,\n                    <jats:italic>Ryr1<\/jats:italic>\n                    expression in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells was dispensable for their pathogenicity in murine models of intestinal inflammation. Thus,\n                    <jats:italic>Ryr1<\/jats:italic>\n                    expression in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells plays a redundant role in intestinal inflammation.\n                  <\/jats:p>","DOI":"10.1002\/eji.70252","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:49:21Z","timestamp":1787035761000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ryanodine Receptor 1 Is Dispensable for CD4\n                    <sup>+<\/sup>\n                    T\u2010Cell Differentiation and Effector Function in Intestinal Inflammation Models"],"prefix":"10.1002","volume":"56","author":[{"given":"Sogol","family":"Dostiar Tabrizi","sequence":"first","affiliation":[{"name":"Section of Molecular Immunology and Gastroenterology, I. Department of Medicine University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"},{"name":"Hamburg Center for Translational Immunology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikolaj","family":"Nawrocki","sequence":"additional","affiliation":[{"name":"Section of Molecular Immunology and Gastroenterology, I. Department of Medicine University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"},{"name":"Hamburg Center for Translational Immunology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Bedke","sequence":"additional","affiliation":[{"name":"Section of Molecular Immunology and Gastroenterology, I. Department of Medicine University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"},{"name":"Hamburg Center for Translational Immunology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"B\u00f6ttcher","sequence":"additional","affiliation":[{"name":"Section of Molecular Immunology and Gastroenterology, I. Department of Medicine University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"},{"name":"Hamburg Center for Translational Immunology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike","family":"Stumme","sequence":"additional","affiliation":[{"name":"Section of Molecular Immunology and Gastroenterology, I. Department of Medicine University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"},{"name":"Hamburg Center for Translational Immunology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melina","family":"Birus","sequence":"additional","affiliation":[{"name":"Hamburg Center for Translational Immunology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"},{"name":"Department of Immunology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"M\u00f6ckl","sequence":"additional","affiliation":[{"name":"The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lola","family":"Hernandez","sequence":"additional","affiliation":[{"name":"The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn\u2010Phillip","family":"Diercks","sequence":"additional","affiliation":[{"name":"The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Gagliani","sequence":"additional","affiliation":[{"name":"Hamburg Center for Translational Immunology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"},{"name":"Department of General, Visceral and Thoracic Surgery University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitri","family":"Lodygin","sequence":"additional","affiliation":[{"name":"Institute For Neuroimmunology and Multiple Sclerosis Research University Medical Center G\u00f6ttingen  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Fl\u00fcgel","sequence":"additional","affiliation":[{"name":"Institute For Neuroimmunology and Multiple Sclerosis Research University Medical Center G\u00f6ttingen  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas H.","family":"Guse","sequence":"additional","affiliation":[{"name":"The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010Willi","family":"Mittr\u00fccker","sequence":"additional","affiliation":[{"name":"Hamburg Center for Translational Immunology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"},{"name":"Department of Immunology University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Huber","sequence":"additional","affiliation":[{"name":"Section of Molecular Immunology and Gastroenterology, I. 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