{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:48:14Z","timestamp":1792187294000,"version":"4.4.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"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>Precisely controlled lymphocyte migration is critically required for immune surveillance and successful immune responses. Lymphocyte migration is strictly regulated by chemokines and chemokine receptors. Here we show that protein geranylgeranylation, a form of post-translational protein lipid modification, is required for chemokine receptor-proximal signaling. Mature thymocytes deficient for protein geranylgeranylation are impaired for thymus egress. Circulating mature T cells lacking protein geranylgeranylation fail to home to secondary lymphoid organs or to transmigrate in response to chemokines <jats:italic>in vitro<\/jats:italic>. Mechanistically, protein geranylgeranylation modifies the \u03b3-subunits of the heterotrimeric small GTPases that are essential for chemokine receptor signaling. In addition, protein geranylgeranylation also promotes the differentiation of IL-17-producing T helper cells while inhibiting the differentiation of Foxp3<jats:sup>+<\/jats:sup> regulatory T cells. Finally, mice with T cell lineage-specific deficiency of protein geranylgeranylation are resistant to experimental autoimmune encephalomyelitis induction. This study elucidated a critical role of protein geranylgeranylation in regulating T lymphocyte migration and function.<\/jats:p>","DOI":"10.3389\/fimmu.2021.641188","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T04:55:42Z","timestamp":1616388942000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["A Requirement of Protein Geranylgeranylation for Chemokine Receptor Signaling and Th17 Cell Function in an Animal Model of Multiple Sclerosis"],"prefix":"10.3389","volume":"12","author":[{"given":"Gregory","family":"Swan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunchong","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanquan","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciana","family":"Walcott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyi J.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-I","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianna Elena","family":"Hammer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2098","DOI":"10.1126\/science.286.5447.2098","article-title":"Chemokines and cell migration in secondary lymphoid organs","volume":"286","author":"Cyster","year":"1999","journal-title":"Science"},{"key":"B2","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1146\/annurev-immunol-032713-120145","article-title":"Chemokines and chemokine receptors: positioning cells for host defense and immunity","volume":"32","author":"Griffith","year":"2014","journal-title":"Annu Rev Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/nature02284","article-title":"Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1","volume":"427","author":"Matloubian","year":"2004","journal-title":"Nature."},{"key":"B4","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/nri3442","article-title":"The integration of T cell migration, differentiation and function","volume":"13","author":"Masopust","year":"2013","journal-title":"Nat Rev Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1056\/NEJM200010053431407","article-title":"T-cell function and migration. 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