{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T04:23:00Z","timestamp":1742962980782,"version":"3.40.3"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1126399; 1189051"],"award-info":[{"award-number":["1126399; 1189051"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p><jats:italic>Plasmodium-<\/jats:italic>specific CD4<jats:sup>+<\/jats:sup> T cells differentiate into effector and memory subsets during experimental malaria, via mechanisms that remain incompletely characterised. By mining scRNA-seq data of CD4<jats:sup>+<\/jats:sup> T cells during <jats:italic>Plasmodium chabaudi chabaudi<\/jats:italic> AS infection in mice, we identified two genes previously uncharacterised in T helper cells, long-tailed unconventional myosin 1f (<jats:italic>Myo1f<\/jats:italic>) and proline-rich13\/taxanes-resistance 1 (<jats:italic>Prr13<\/jats:italic>\/<jats:italic>Txr1<\/jats:italic>), which were upregulated during effector and memory differentiation. Myo1f is reported to regulate motility and granule exocytosis in myeloid and \u03b3\u03b4 T cells. Prr13\/Txr1 is reported to transcriptionally regulate sensitivity to anti-cancer drugs. To test for cell-intrinsic gene function, we generated <jats:italic>Plasmodium-<\/jats:italic>specific TCR transgenic, PbTII cells harbouring CD4-promoter driven Cre recombinase and target genes with <jats:italic>loxP<\/jats:italic>-flanked essential exons. We validated our approach for the transcription factor <jats:italic>Maf<\/jats:italic>, formally demonstrating here that cMaf is essential for T follicular helper (Tfh) cell differentiation in experimental malaria. Next, having generated conditional knockout lines for <jats:italic>Myo1f<\/jats:italic> and <jats:italic>Prr13,<\/jats:italic> we observed that deficiency in <jats:italic>Myo1f<\/jats:italic> or <jats:italic>Prr13<\/jats:italic> had no impact on either clonal expansion, Th1\/Tfh differentiation or transit to memory. Additionally, despite continued expression during re-infection, <jats:italic>Myo1f<\/jats:italic> was unnecessary for Th1 recall <jats:italic>in vivo<\/jats:italic>. Thus, while cMaf is critical for Tfh differentiation in experimental malaria, <jats:italic>Myo1f<\/jats:italic> and <jats:italic>Prr13<\/jats:italic>, although transcriptionally upregulated, are unnecessary for effector or memory CD4<jats:sup>+<\/jats:sup> T cell responses.<\/jats:p>","DOI":"10.1371\/journal.pone.0320375","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T22:57:58Z","timestamp":1742943478000},"page":"e0320375","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Myosin 1f and Proline-rich 13 are transcriptionally upregulated yet functionally redundant in CD4+ T cells during blood-stage Plasmodium infection"],"prefix":"10.1371","volume":"20","author":[{"given":"Takahiro","family":"Asatsuma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela L.","family":"Moreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun J.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brooke J.","family":"Wanrooy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver P.","family":"Skinner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shihan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Rea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taidhgin","family":"Harkin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saba","family":"Asad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cameron G.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynette","family":"Beattie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2260-0026","authenticated-orcid":true,"given":"Ashraful","family":"Haque","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"key":"pone.0320375.ref001","unstructured":"WHO. 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