{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:44:28Z","timestamp":1791499468510,"version":"4.3.4"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pregnancy requires precise maternal immune adaptation to support fetal development while maintaining defense against external threats. Disruption of this balance can result in complications such as preeclampsia (PE), a major cause of maternal and fetal morbidity and mortality. Low\u2010dose aspirin (LDA) is widely used to prevent PE, but its immunomodulatory mechanisms are not fully understood. In this observational study (CES\u2010BS_SF_160_2022; NCT06882850), 32 healthy pregnant women were enrolled and PE risk assessed; 16 classified as high\u2010risk received LDA (150\u2009mg\/day) from the first trimester until 36\u2009weeks, and 16 served as controls. Peripheral blood was collected in each trimester (T1, T2, T3), with an additional sample 4\u2009weeks after LDA initiation in the Risk Group (T1.2). Complete blood counts and flow cytometry assessed immune cell populations. Both groups were well\u2010matched for maternal, delivery, and neonatal characteristics, with no significant differences in complications or adverse outcomes. White blood cell subpopulations did not differ significantly. However, the Risk Group had significantly lower haemoglobin and platelet levels in the second trimester. T cell frequencies increased in the Risk Group by the second trimester, with higher percentages of CD4 and CD8 T cells. NK cell analysis showed a decrease in total NK cells at the second trimester versus 4\u2009weeks after LDA initiation, with an increase in CD56\n                    <jats:sup>bright<\/jats:sup>\n                    (tolerogenic) NK cells and a decrease in CD56\n                    <jats:sup>dim<\/jats:sup>\n                    (cytotoxic) NK cells. Regulatory T cell (Treg) analysis revealed increased na\u00efve and activated (HLA\u2010DR\n                    <jats:sup>+<\/jats:sup>\n                    ) Treg cells and decreased memory Treg cells at the second trimester. Activated (HLA\u2010DR\n                    <jats:sup>+<\/jats:sup>\n                    ) Th17 and Th17.1 cells were lower in the Risk Group at the second trimester. These results suggest that LDA in high\u2010risk pregnancies is associated with lower haemoglobin and platelet levels, an increase in na\u00efve Treg cells, and a shift from cytotoxic to tolerogenic NK cells. The decline in activated Th17 and Th17.1 cells indicates enhanced immune tolerance and reduced inflammation, supporting LDA's role in modulating immune responses to promote healthy pregnancy outcomes. Importantly, these findings should be interpreted as hypothesis\u2010generating; the limited sample size and single\u2010center design constrain the strength of clinical inferences and underscore the need for replication in larger, multicenter cohorts. Further research is needed to determine whether these immunological changes correlate with improved clinical outcomes in broader populations.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                    : NCT06882850\n                  <\/jats:p>","DOI":"10.1111\/imm.70051","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T03:32:09Z","timestamp":1760499129000},"page":"329-338","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Modulation of Immune Cells by Aspirin During Pregnancy"],"prefix":"10.1111","volume":"177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2371-8907","authenticated-orcid":false,"given":"Ana Lu\u00edsa","family":"Areia","sequence":"first","affiliation":[{"name":"Obstetrics Department Coimbra University Hospitals\u2014Coimbra Local Health Care Unit  Coimbra Portugal"},{"name":"Faculty of Medicine University of Coimbra  Coimbra Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine University of Coimbra"},{"name":"Centre of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Biomarkers &amp; Inflammation Group, Faculty of Medicine University of Coimbra  Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jani","family":"Almeida","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Coimbra  Coimbra Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine University of Coimbra"},{"name":"Centre of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Biomarkers &amp; Inflammation Group, Faculty of Medicine University of Coimbra  Portugal"},{"name":"Institute of Immunology\u2014Faculty of Medicine University of Coimbra"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Alves","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Coimbra  Coimbra Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine University of Coimbra"},{"name":"Centre of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Biomarkers &amp; Inflammation Group, Faculty of Medicine University of Coimbra  Portugal"},{"name":"Institute of Immunology\u2014Faculty of Medicine University of Coimbra"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anabela","family":"Mota\u2010Pinto","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Coimbra  Coimbra Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine University of Coimbra"},{"name":"Centre of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Biomarkers &amp; Inflammation Group, Faculty of Medicine University of Coimbra  Portugal"},{"name":"Institute of General Pathology\u2014Faculty of Medicine University of Coimbra"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"S\u00e1","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Coimbra  Coimbra Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine University of Coimbra"},{"name":"Centre of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Biomarkers &amp; Inflammation Group, Faculty of Medicine University of Coimbra  Portugal"},{"name":"Nephrology Department Coimbra University Hospitals\u2014Coimbra Local Health Care Unit  Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2020.07.013"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0296434"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.550543"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02025"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100036\u20101582397"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00261"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2019.4814"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina58020157"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109\u2010018\u20101695\u20109"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.08.010"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa642"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2019.01.222"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2021.11.019"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0254606"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm\u201022\u2010735"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3109\/10641955.2014.931419"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.793107"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1615\/critrevimmunol.v32.i1.30"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijgo.12802"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.19039"},{"key":"e_1_2_12_22_1","unstructured":"Foundation TFM \u201cRisk for Preeclampsia \u201dhttps:\/\/fetalmedicine.org\/research\/assess\/preeclampsia\/first\u2010trimester."},{"key":"e_1_2_12_23_1","unstructured":"NICE NIfHaCE \u201c\u2018Hypertension in Pregnancy: Diagnosis and Management\u2019. 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