{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:04:21Z","timestamp":1784610261700,"version":"3.55.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"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>Background<\/jats:title>\n                    <jats:p>Myeloid cells can express lymphoid markers, including components of the CD3-TCR complex. CD3+ macrophages have been identified in both infectious and non-infectious pathologies; however, their origin and signaling mechanisms remain poorly studied, primarily due to their low prevalence in human samples. Utilizing the RAW murine macrophage cell line as a model, this study aimed to ascertain whether nutrient deprivation induces CD3 expression and to identify the signaling molecules involved in the activation of a CD3-dependent proinflammatory profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Firstly, the impact of environmental stress, specifically nutrient deprivation, on CD3 expression over a period was assessed. Subsequently, RAW cells were stimulated with anti-CD3 and IgG2a, and the profile of proinflammatory cytokines was evaluated alongside the expression of signaling proteins, including NFAT, c-Jun, and IKK. Furthermore, the transcriptional regulation of\n                      <jats:italic>IRF-1<\/jats:italic>\n                      ,\n                      <jats:italic>GATA-3<\/jats:italic>\n                      , and\n                      <jats:italic>MAFB<\/jats:italic>\n                      was examined. Lastly, the functional capacity of CD3+ RAW cells was determined through a phagocytosis assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>RAW cells were found to express molecules classically associated with T cells, including CD3, TCR, and CD4. Notably, CD3 expression was significantly upregulated at both the protein and transcriptional levels under nutrient deprivation, although it did not reach the levels observed in T cells. Functionally, CD3+ RAW cells exhibited enhanced phagocytic activity toward latex beads. Furthermore, stimulation with anti-CD3 plus IgG2a induced a robust proinflammatory cytokine response, characterized by the secretion of IFN-\u03b3, TNF, and IL-6 as early as 5 hours post-stimulation. This response was associated with activation of signaling pathways involving NFAT, c-Jun, and IKK, along with increased IRF-1 expression and downregulation of MAFB, supporting the establishment of a CD3-dependent proinflammatory profile in RAW cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings establish RAW macrophages as a model to study CD3+ signaling machinery in myeloid cells. We demonstrate for the first time that nutrient deprivation induces CD3 expression and that the resulting CD3-driven proinflammatory program is associated, at least in part, with NFAT and\n                      <jats:italic>IRF-1<\/jats:italic>\n                      . These conclusions provide new insights into the origin and functional significance of CD3+ macrophages and offer a valuable platform for investigating the impact of this pathway on innate immune responses across various pathological contexts.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1857007","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:20:22Z","timestamp":1784607622000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Nutrient deprivation increases CD3 expression in RAW cells and augments the CD3-induced proinflammatory profile, associated with NFAT and IRF-1"],"prefix":"10.3389","volume":"17","author":[{"given":"Ranferi","family":"Oca\u00f1a-Guzman","sequence":"first","affiliation":[{"name":"Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucero A.","family":"Ramon-Luing","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jahir","family":"Mendoza-Ruiz","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"L\u00f3pez-Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alondra","family":"Hern\u00e1ndez-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Yarelli","family":"Huerta-Zarco","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Flores-Gonzalez","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Chavez-Galan","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas","place":["Mexico City, 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