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The spatial organization of CD40 on the dendritic cell surface is thought to dictate its signaling output, yet the underlying mechanisms are poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Fluorescently tagged BMDCs were generated via lentiviral transduction of CD40-mGFP and electroporation of LifeAct-eGFP constructs. BMDCs, derived from C57BL\/6\u00a0J mice and matured with LPS, were co-cultured with na\u00efve OT-II CD4\u207a T cells or functionalized beads to model immunological synapses. Pseudo-synapse formation and CD40 recruitment were analyzed using TIRF, confocal, and dSTORM super-resolution microscopy, with actin dynamics and membrane protein mobility assessed via live-cell imaging and FRAP. Surface protein expression, cell viability, and cytokine secretion were quantified by flow cytometry and ELISA. Super-resolution data were analyzed using density-based clustering and Ripley\u2019s L-function to quantify spatial organization. Statistical comparisons were performed using Student\u2019s t-tests or one- and two-way ANOVA, with significance thresholds set at\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.05.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We show that dendritic cell maturation first remodels the nanoscale clustering of CD40. Upon immunological synapse formation and CD40L engagement, CD40 is concentrated into a stable central cluster. We demonstrate that this centralization is not driven by global actin flow but by a specific restriction of CD40's lateral mobility at the synapse center. We identify contractile actomyosin rings, marked by \u03b1-actinin-4 and phosphorylated myosin light chain, encircling CD40. CD40 ligation increases myosin IIA activity, and pharmacological inhibition of this activity abrogates both the integrity of these rings and CD40 centralization. Functionally, disrupting this spatial organization selectively impairs the p38 MAPK pathway and the upregulation of costimulatory ligands CD70 and OX40L.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings reveal a myosin IIA-dependent mechanism that organizes CD40 to fine-tune dendritic cell licensing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12964-026-02816-0","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T04:46:25Z","timestamp":1776487585000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Actomyosin rings constrain CD40 mobility to organize the dendritic cell immunological synapse"],"prefix":"10.1186","volume":"24","author":[{"given":"Camille D.","family":"Clamagirand","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliane","family":"Mallet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Nieves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Ratswohl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan M.","family":"Owen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9mie","family":"Rossy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"issue":"11","key":"2816_CR1","doi-asserted-by":"publisher","first-page":"5786","DOI":"10.4049\/jimmunol.163.11.5786","volume":"163","author":"A Aicher","year":"1999","unstructured":"Aicher A, Shu GL, Magaletti D, et al. 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