{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:26:37Z","timestamp":1787030797915,"version":"build-2736575974"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Tissue-derived chemokines can direct immune cell migration by engaging specific receptors, thereby controlling the localization and trafficking of immune cells within tissues. However, how chemokines modulate cytokines-driven transcriptional programs in T cells remain unclear. This study investigated how CXCL8 and CCL20 influence human T cell responses to IL-15 and IL-32\u03b1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Peripheral blood T cells from health donors were evaluated for the expression and functional activity of the chemokine receptors CCR6, CXCR1, and CXCR2. Chemokine induced migration was assessed using\n                      <jats:italic>in vitro<\/jats:italic>\n                      migration assays. T cells were stimulated with CCL20 or CXCL8 alone or in combination with IL-15 or IL-32\u03b1, and transcriptional responses were characterized by transcriptomic profiling. Selected transcriptional findings were further evaluated through functional and protein-level assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Peripheral blood T cells expressed CCR6, CXCR1, and CXCR2, which were downregulated during\n                      <jats:italic>vitro<\/jats:italic>\n                      culture, but remained functionally responsive in migration assays, highlighting the influence of the microenvironmental on receptor expression. Transcriptomic profiling showed that CCL20 and CXCL8 independently reprogrammed GPCR-associated networks involved in migration, cytoskeletal dynamics, adhesion, and chemokine scavenging. IL-15 induced robust JAK\/STAT-dependent inflammatory and survival programs together with CISH upregulation, indicating coordinated activation and negative-feedback regulation. In contrast, IL-32\u03b1 modulated PI3K\/AKT, adhesion, and NOTCH1-related pathways and was associated with increased T cell proliferation. Combined stimulation revealed context-dependent integration of these signaling programs. IL-15 plus CCL20 enhanced inflammatory and migratory signatures, whereas CXCL8 plus IL-15 produced a transcriptional profile largely dominated by IL-15. IL-32\u03b1 plus CXCL8 induced cooperative programs involving vesicular remodeling, mTOR-associated metabolism, cytoskeletal organization, and cell-cycle regulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings demonstrated that chemokine and cytokine signals are integrated in a context-dependent manner to regulate T cells migration, activation, survival and proliferation. Rather than acting solely as chemoattractant, CCL20 and CXCL8 can reshape cytokine-driven transcriptional profile programs, revealing additional regulatory layer that may contribute to T cell functional plasticity within inflammatory and tumor microenvironment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1910983","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:28:07Z","timestamp":1787027287000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic integration of CXCL8 or CCL20 signaling with IL-15 or IL-32\u03b1 reprograms human T-cell functional plasticity"],"prefix":"10.3389","volume":"17","author":[{"given":"Messias de Oliveira","family":"Pacheco","sequence":"first","affiliation":[{"name":"Faculdade Israelita de Ci\u00eancias da Sa\u00fade Albert Einstein, Hospital Israelita Albert Einstein - Department of Experimental 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