{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T17:47:06Z","timestamp":1792259226215,"version":"4.4.0"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T00:00:00Z","timestamp":1672185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Problems<\/jats:title>\n                    <jats:p>Maternal chronic inflammation (MI) can adversely affect offspring's immune development resulting in dysregulation of splenic T cells. Interleukin 1 beta (IL\u20101\u03b2) contributes to mediating inflammation in the placenta to induce fetal toxicity and cause long\u2010term postnatal sequelae. In this study, we investigated how MI affects the T\u2010cell immune development from the fetal to the neonatal period and how offspring responded to postnatal IL\u20101\u03b2 challenge when exposed to an adverse intrauterine environment. We also extend these studies to examine the sex\u2010specific differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods of Study<\/jats:title>\n                    <jats:p>Time\u2010pregnant CD1 dams were administrated with four consecutive injections of mouse recombinant Interleukin\u20101\u03b2 (rIL\u20101\u03b2) or phosphate\u2010buffered saline (PBS) from embryonic day (E)14 to E17. Pups were treated with rIL\u20101\u03b2 or PBS at postnatal day (PND)11 (pre\u2010weaning) or PND24 (post\u2010weaning). Pups\u2019 splenic immune cells were isolated and then characterized using flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At PND12, no differences were observed either in Ctrl or MI offspring. At PND25, we observed elevated amount of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, descending CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      and Treg\/Teff ratio in MI offspring. Pre\u2010weaning rIL\u20101\u03b2 administration did not affect T\u2010cell subpopulation in Ctrl pups while post\u2010weaning rIL\u20101\u03b2 administration increased T cells and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and decreased CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      and Treg\/Teff ratio in Ctrl offspring. Furthermore, pre\u2010weaning rIL\u20101\u03b2 administration decreased the frequency of T cells and Treg\/Teff ratio in MI pups while post\u2010weaning rIL\u20101\u03b2 administration increased Tregs and Treg\/Teff in MI pups. Regarding sex\u2010specific changes, we observed that at PND12, MI females exhibited higher CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      and Treg\/Teff ratio than Ctrl females. At PND25, we observed elevated amount of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, descending CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      and Treg\/Teff ratio in MI Females, while MI males did not show any changes in T\u2010cell population. Pre\u2010weaning rIL\u20101\u03b2 administration decreased T\u2010cell frequency in both MI males and females and decreased Treg\/Teff ratio only in MI females. Post\u2010weaning rIL\u20101\u03b2 administration increased Tregs and Treg\/Teff ratio, and decreased CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      ratio in MI females.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Prenatal\u2010inflammation\u2010exposed offspring exhibited dysfunctional T\u2010cell immunity and regulatory immune responses to postnatal challenges, showing both sex\u2010specific and age\u2010dependent differences. It could be speculated from our results that experiencing environmental challenges or adverse stimuli during the vulnerable intrauterine period, such as maternal chronic inflammation, stress, preterm birth, and chronic infections, might induce fetal immune reprogramming and potentially cause long\u2010term adverse immune consequences, such as a predisposition to allergic diseases, autoimmune diseases, asthma and pediatric mortality of unknown etiology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aji.13665","type":"journal-article","created":{"date-parts":[[2022,12,11]],"date-time":"2022-12-11T23:09:25Z","timestamp":1670800165000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Sex\u2010specific differences in T\u2010cell immune dysregulation and aberrant response to inflammatory stimuli in offspring exposed to maternal chronic inflammation"],"prefix":"10.1111","volume":"89","author":[{"given":"Jin","family":"Liu","sequence":"first","affiliation":[{"name":"Integrated Research Center for Fetal Medicine Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Integrated Research Center for Fetal Medicine Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Kirschen","sequence":"additional","affiliation":[{"name":"Integrated Research Center for Fetal Medicine Department of Gynecology and Obstetrics Johns Hopkins University School of Medicine  Baltimore Maryland 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