{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:09:07Z","timestamp":1789711747693,"version":"4.0.1"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"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>Maternal immune activation (MIA) is associated with increased risk for neurodevelopmental disorders, including schizophrenia and autism spectrum disorder, yet its long-term impact on intestinal immune-microbial programming remains incompletely understood. Here, we investigated whether lipopolysaccharide (LPS)\u2013induced MIA drives persistent alterations in the offspring mucosal immune environment, with a focus on intraepithelial lymphocytes, mucosa-associated microbiota, systemic cytokines, and prefrontal cortical immune-related readouts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MIA was induced in wild-type BALB\/cByJ mice via intraperitoneal LPS injection at gestational day 12.5. Male and female offspring were assessed at 10 weeks of age for gut, systemic, and prefrontal cortex (PFC) immune alterations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MIA offspring displayed a regionally restricted intestinal immune signature, with more pronounced alterations in the ileum than in the colon. Ileal changes included increased inflammatory cytokine signaling and remodeling of IEL populations, particularly TCR\u03b3\u03b4 CD8\u03b1\u03b1 cells, together with changes in TCR\u03b1\u03b2 IEL subsets. Analysis of the mucosa-associated microbiome revealed parallel changes in ileal microbial community structure, including alterations in segmented filamentous bacteria and\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      . These mucosal alterations co-occurred with increased plasma IL-6 in both female and male offspring, while plasma IL-17 was selectively increased in females. In the PFC, MIA was associated with cytokine changes and divergent microglial morphological profiles, suggesting that prenatal immune challenge produces neuroimmune alterations that may differ in sex, timing, magnitude, or cellular expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Collectively, these findings identify the mucosa-associated microbiota-IEL interface as a previously underexplored component of MIA-induced immune remodeling. Our study provides an integrated framework in which persistent ileal immune and microbial alterations co-occur with systemic inflammation and cortical neuroimmune changes in MIA offspring, supporting future mechanistic studies of gut\u2013brain immune communication in neurodevelopmental disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1945751","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:38:35Z","timestamp":1789709915000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mucosal microbiota and intraepithelial lymphocyte remodeling link maternal immune activation to neuroimmune outcomes in female and male offspring"],"prefix":"10.3389","volume":"17","author":[{"given":"Ana Raquel","family":"Pereira-Santos","sequence":"first","affiliation":[{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra","place":["Coimbra, 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Portugal"]},{"name":"Faculty of Medicine, University of Coimbra (FMUC)","place":["Coimbra, Portugal"]},{"name":"Center for Investigation in Environment, Genetics and Oncobiology, University of Coimbra","place":["Coimbra, Portugal"]},{"name":"Clinical and Academic Centre of Coimbra (CACC), ULS of Coimbra","place":["Coimbra, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuno","family":"Empadinhas","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra","place":["Coimbra, Portugal"]},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra","place":["Coimbra, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra Morais","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology (CNC), University of Coimbra","place":["Coimbra, Portugal"]},{"name":"Centre for Innovative Biomedicine and 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