{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:56:21Z","timestamp":1790128581675,"version":"4.0.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["5R01-AI125513-05"],"award-info":[{"award-number":["5R01-AI125513-05"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>During T cell development, heterogeneous nuclear ribonucleoprotein (hnRNP) L is known to regulate CD4 T helper subset differentiation, the proliferation and migration of thymocytes, as loss of hnRNP L in early T cell development results in a failure of T cells to reach the periphery. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To better understand the role of hnRNP L in modulating peripheral T cell trafficking and function, we analyzed T survival and activation in newly generated CD4Cre x hnRNP L<jats:sup>Fl\/Fl<\/jats:sup> (KO) mice. <jats:italic>In vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> analyses of CD4 T cell differentiation, T cell proliferation and death post activation were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our initial study of the steady state profile of the KO mice showed normal migration of T cells from the thymus, but peripheral T cell numbers were reduced. Analysis of TCR-mediated signaling pathways revealed normal early T cell activation. However, T cells lacking hnRNP L had marked defects in their ability to differentiate into T helper cell subsets due to reduced proliferation and increased death. In vivo, using immunization studies, KO CD4 T cells failed to fully differentiate into T follicular helper (Tfh) cells and were unable to support the formation of germinal center B cells. Death of activated hnRNP L KO cells could be reversed by treating the cells with zVAD, a pan-caspase inhibitor. In addition, hnRNP L KO cells failed to upregulate the anti-apoptotic protein Bcl-XL following activation. <\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These studies suggest that hnRNP L plays an important role in T cell activation and survival. Our studies suggest that hnRNP L plays a critical pro-survival role in activated T cells and that alternative splicing of factors that prevent apoptosis may be an important mechanism by which this is achieved.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1543145","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T05:11:20Z","timestamp":1744261880000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["HnRNP L is essential for peripheral T cell proliferation and survival"],"prefix":"10.3389","volume":"16","author":[{"given":"Tristan L. A.","family":"White","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin J.","family":"Henry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean D. 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