{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:30:30Z","timestamp":1787725830250,"version":"build-2784847793"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"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                    p38\u03b3 and p38\u03b4 (p38\u03b3\/p38\u03b4) have emerged as important regulators of immune function; however, their specific contribution to adaptive humoral responses remains poorly understood. Based on previous evidence that global p38\u03b3\/p38\u03b4 deficiency impairs antibody production, we investigated the T cell-intrinsic role of these kinases using conditional knockout mouse models. T cell-specific combined deletion of p38\u03b3 and p38\u03b4 altered antigen-specific IgG subclass production\n                    <jats:italic>in vivo<\/jats:italic>\n                    , causing transient reductions in IgG2b and IgG3 and a persistent decrease in IgG2a titres. This defect correlated with impaired activation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, reduced generation of effector T cells, and a significant decrease in T follicular helper (Tfh) cell differentiation. Gene expression analyses revealed diminished levels of key Tfh-associated cytokines, including\n                    <jats:italic>Il21<\/jats:italic>\n                    ,\n                    <jats:italic>Il4<\/jats:italic>\n                    ,\n                    <jats:italic>Cxcl13<\/jats:italic>\n                    , and\n                    <jats:italic>Il10<\/jats:italic>\n                    . Together, these findings demonstrate that p38\u03b3\/p38\u03b4 signalling in T cells is essential for Tfh differentiation, cytokine production, and effective T cell-dependent humoral immunity, including the generation of class-switched IgG antibodies, particularly IgG2 subclasses.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1927358","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:04:18Z","timestamp":1787724258000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["p38\u03b3 and p38\u03b4 support CD4+ T cell responses and T cell-dependent humoral immunity"],"prefix":"10.3389","volume":"17","author":[{"given":"Diego","family":"Gonz\u00e1lez-Romero","sequence":"first","affiliation":[{"name":"Department of Immunology and Oncology, Centro Nacional de Biotecnolog\u00eda (CNB)\/CSIC","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"D\u00edaz-Mora","sequence":"additional","affiliation":[{"name":"Department of Immunology and Oncology, Centro Nacional de Biotecnolog\u00eda (CNB)\/CSIC","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Fajardo","sequence":"additional","affiliation":[{"name":"Department of Immunology and Oncology, Centro Nacional de Biotecnolog\u00eda (CNB)\/CSIC","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Jos\u00e9","family":"Sanz-Ezquerro","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, CNB\/CSIC","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda R.","family":"Carrasco","sequence":"additional","affiliation":[{"name":"B Lymphocyte Dynamics, Department of Immunology and Oncology, CNB\/CSIC","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Cuenda","sequence":"additional","affiliation":[{"name":"Department of Immunology and Oncology, Centro Nacional de Biotecnolog\u00eda (CNB)\/CSIC","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2017.02.008","article-title":"p38\u03b3 and p38\u03b4: From spectators to key physiological players","volume":"42","author":"Cuenda","year":"2017","journal-title":"Trends Biochem Sci"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201708485","article-title":"Myeloid cell deficiency of p38\u03b3\/p38\u03b4 protects against candidiasis and regulates antifungal immunity","volume":"10","author":"Alsina-Beauchamp","year":"2018","journal-title":"EMBO Mol 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