{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T06:44:38Z","timestamp":1778136278519,"version":"3.51.4"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T00:00:00Z","timestamp":1727049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100012264","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AI131337"],"award-info":[{"award-number":["U01 AI131337"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI127695"],"award-info":[{"award-number":["R01AI127695"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K12HD000850"],"award-info":[{"award-number":["K12HD000850"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K12HD111057"],"award-info":[{"award-number":["K12HD111057"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In humans and in mice, maternal allergy predisposes offspring to development of allergy. In murine models, increased levels of maternal \u03b2-glucosylceramides are both necessary and sufficient for the development of allergic predisposition in offspring. Furthermore, increased numbers of CD11b+ dendritic cell subsets in the offspring of allergic mothers are associated with allergic predisposition. In vitro, \u03b2-glucosylceramides increase CD11b+ dendritic cell subset numbers through increased PKC\u03b4 signaling, but it is not known if enhanced PKC\u03b4 signaling in dendritic cells is required in vivo. We demonstrate that dendritic cell\u2013specific deletion of PKC\u03b4 prevents the \u03b2-glucosylceramide\u2013induced increase in CD11b+ dendritic cell subset numbers both in vitro as well as in vivo in the fetal liver of offspring of mothers injected with \u03b2-glucosylceramides. Furthermore, dendritic cell\u2013specific deletion of PKC\u03b4 in offspring prevents the maternal allergy\u2013induced increase in CD11b+ dendritic cell subsets and decreases allergen-induced interleukin-5 and eosinophilia in lungs of offspring. However, loss of PKC\u03b4 in dendritic cells did not prevent development of allergen-specific IgE. Our study provides mechanistic insight into the function of PKC\u03b4 in the origins of allergic disease beginning in utero as well as in the development of postnatal allergic lung inflammation.<\/jats:p>","DOI":"10.1093\/jleuko\/qiae207","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T18:54:47Z","timestamp":1727117687000},"page":"1432-1445","source":"Crossref","is-referenced-by-count":1,"title":["Dendritic cell\u2013specific deletion of PKC\u03b4 in offspring of allergic mothers prevents the predisposition for development of allergic lung inflammation in offspring"],"prefix":"10.1093","volume":"116","author":[{"given":"Jacquelyn D","family":"Lajiness","sequence":"first","affiliation":[{"name":"Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Indiana University School of Medicine , Indianapolis, IN 46202 ,","place":["United States"]},{"name":"Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine , Indianapolis, IN 46202 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey C","family":"Bloodworth","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, IN 46202 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ross L","family":"Blankenship","sequence":"additional","affiliation":[{"name":"Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine , Indianapolis, IN 46202 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison E","family":"Kosins","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, IN 46202 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1564-5218","authenticated-orcid":false,"given":"Joan M","family":"Cook-Mills","sequence":"additional","affiliation":[{"name":"Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine , Indianapolis, IN 46202 ,","place":["United States"]},{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, IN 46202 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,9,23]]},"reference":[{"issue":"1","key":"2024112705082867400_qiae207-B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1600-0897.2008.00671.x","article-title":"Maternal transmission of asthma risk","volume":"61","author":"Lim","year":"2009","journal-title":"Am J Reprod Immunol"},{"issue":"4","key":"2024112705082867400_qiae207-B2","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.4049\/jimmunol.170.4.1683","article-title":"Allergen-independent maternal transmission of asthma susceptibility","volume":"170","author":"Hamada","year":"2003","journal-title":"J Immunol"},{"issue":"2","key":"2024112705082867400_qiae207-B3","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1111\/j.1600-0897.2007.00496.x","article-title":"Duration of allergic susceptibility in maternal transmission of asthma risk","volume":"58","author":"Fedulov","year":"2007","journal-title":"Am J Reprod Immunol"},{"issue":"3","key":"2024112705082867400_qiae207-B4","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.4049\/jimmunol.178.3.1477","article-title":"Targeting of cd25 and glucocorticoid-induced tnf receptor family-related gene-expressing t cells differentially modulates asthma risk in offspring of asthmatic and normal mother mice","volume":"178","author":"Hubeau","year":"2007","journal-title":"J Immunol"},{"issue":"6","key":"2024112705082867400_qiae207-B5","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.2353\/ajpath.2006.051231","article-title":"Adoptively transferred allergen-specific t cells cause maternal transmission of asthma risk","volume":"168","author":"Hubeau","year":"2006","journal-title":"Am J Pathol"},{"issue":"1-3","key":"2024112705082867400_qiae207-B6","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1159\/000053708","article-title":"Allergic sensitization and allergen exposure during pregnancy favor the development of atopy in the neonate","volume":"124","author":"Herz","year":"2001","journal-title":"Int Arch Allergy Immunol"},{"issue":"3 Pt 2","key":"2024112705082867400_qiae207-B7","doi-asserted-by":"publisher","first-page":"S62","DOI":"10.1164\/ajrccm.162.supplement_2.ras-1","article-title":"Prenatal sensitization in a mouse model","volume":"162","author":"Herz","year":"2000","journal-title":"Am J Respir Crit Care Med"},{"issue":"5718","key":"2024112705082867400_qiae207-B8","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1038\/280145a0","article-title":"Selective suppression of IgE antibody responsiveness by maternal influence","volume":"280","author":"Jarrett","year":"1979","journal-title":"Nature"},{"issue":"5","key":"2024112705082867400_qiae207-B9","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1016\/j.jaci.2018.02.003","article-title":"Mechanism for initiation of food allergy: dependence on skin barrier mutations and environmental allergen costimulation","volume":"141","author":"Walker","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"2024112705082867400_qiae207-B10","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.freeradbiomed.2021.10.037","article-title":"Asthma, allergy and vitamin E: current and future perspectives","volume":"179","author":"Cook-Mills","year":"2022","journal-title":"Free Radic Biol Med"},{"issue":"6","key":"2024112705082867400_qiae207-B11","doi-asserted-by":"publisher","first-page":"L482","DOI":"10.1152\/ajplung.00132.2014","article-title":"\u0391-tocopherol supplementation of allergic female mice inhibits development of CD11C+CD11B+ dendritic cells in utero and allergic inflammation in neonates","volume":"307","author":"Abdala-Valencia","year":"2014","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"8","key":"2024112705082867400_qiae207-B12","doi-asserted-by":"publisher","first-page":"L759","DOI":"10.1152\/ajplung.00301.2015","article-title":"\u03b3-Tocopherol supplementation of allergic female mice augments development of CD11C+CD11B+ dendritic cells in utero and allergic inflammation in neonates","volume":"310","author":"Abdala-Valencia","year":"2016","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"3","key":"2024112705082867400_qiae207-B13","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1165\/rcmb.2009-0400OC","article-title":"Allergy risk is mediated by dendritic cells with congenital epigenetic changes","volume":"44","author":"Fedulov","year":"2011","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"10","key":"2024112705082867400_qiae207-B14","doi-asserted-by":"publisher","first-page":"1837","DOI":"10.4049\/jimmunol.2101188","article-title":"\u03b2-Glucosylceramides and tocopherols regulate development and function of dendritic cells","volume":"209","author":"Lajiness","year":"2022","journal-title":"J Immunol"},{"key":"2024112705082867400_qiae207-B15","doi-asserted-by":"publisher","first-page":"647134","DOI":"10.3389\/falgy.2021.647134","article-title":"\u03b2-Glucosylceramide from allergic mothers enhances offspring responsiveness to allergen","volume":"2","author":"Walker","year":"2021","journal-title":"Front Allergy"},{"issue":"7","key":"2024112705082867400_qiae207-B16","doi-asserted-by":"publisher","first-page":"e0253912","DOI":"10.1371\/journal.pone.0253912","article-title":"PKC\u03b4 deficiency inhibits fetal development and is associated with heart elastic fiber hyperplasia and lung inflammation in adult PKC\u03b4 knockout mice","volume":"16","author":"Niino","year":"2021","journal-title":"PLoS One"},{"issue":"7","key":"2024112705082867400_qiae207-B17","doi-asserted-by":"publisher","first-page":"4395","DOI":"10.4049\/jimmunol.0803659","article-title":"Isoforms of vitamin E have opposing immunoregulatory functions during inflammation by regulating leukocyte recruitment","volume":"182","author":"Berdnikovs","year":"2009","journal-title":"J Immunol"},{"issue":"7","key":"2024112705082867400_qiae207-B18","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1084\/jem.20062648","article-title":"Notch-RBP-J signaling controls the homeostasis of CD8- dendritic cells in the spleen","volume":"204","author":"Caton","year":"2007","journal-title":"J Exp Med"},{"key":"2024112705082867400_qiae207-B19","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.jim.2014.05.009","article-title":"Comparative analysis of the efficiency and specificity of myeloid-Cre deleting strains using ROSA-EYFP reporter mice","volume":"408","author":"Abram","year":"2014","journal-title":"J Immunol Methods"},{"issue":"1","key":"2024112705082867400_qiae207-B20","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1471-213x-1-4","article-title":"Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus","volume":"1","author":"Srinivas","year":"2001","journal-title":"BMC Dev Biol"},{"issue":"16","key":"2024112705082867400_qiae207-B21","doi-asserted-by":"publisher","first-page":"2096","DOI":"10.3390\/cells12162096","article-title":"Variable Cre recombination efficiency in placentas of Cyp19-Cre ROSAmT\/mG transgenic mice","volume":"12","author":"Anamthathmakula","year":"2023","journal-title":"Cells"},{"issue":"11","key":"2024112705082867400_qiae207-B22","doi-asserted-by":"publisher","first-page":"2550","DOI":"10.1161\/atvbaha.118.309669","article-title":"Endothelial-specific Cre mouse models","volume":"38","author":"Payne","year":"2018","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"12","key":"2024112705082867400_qiae207-B23","doi-asserted-by":"publisher","first-page":"3224","DOI":"10.1016\/j.ajpath.2015.08.002","article-title":"ADAR1 prevents liver injury from inflammation and suppresses interferon production in hepatocytes","volume":"185","author":"Wang","year":"2015","journal-title":"Am J Pathol"},{"issue":"2","key":"2024112705082867400_qiae207-B24","doi-asserted-by":"publisher","first-page":"100080","DOI":"10.1016\/j.waojou.2019.100080","article-title":"IgE allergy diagnostics and other relevant tests in allergy, a world allergy organization position paper","volume":"13","author":"Ansotegui","year":"2020","journal-title":"World Allergy Organ J"},{"issue":"9","key":"2024112705082867400_qiae207-B25","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s11882-015-0556-7","article-title":"Molecular allergy diagnostics: analytical features that support clinical decisions","volume":"15","author":"Hamilton","year":"2015","journal-title":"Curr Allergy Asthma Rep"},{"issue":"6","key":"2024112705082867400_qiae207-B26","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1016\/j.jaip.2015.08.016","article-title":"Serological IgE analyses in the diagnostic algorithm for allergic disease","volume":"3","author":"Hamilton","year":"2015","journal-title":"J Allergy Clin Immunol Pract"},{"issue":"11","key":"2024112705082867400_qiae207-B27","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/s2213-2600(15)00367-7","article-title":"Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study","volume":"3","author":"Price","year":"2015","journal-title":"Lancet Respir Med"},{"issue":"15","key":"2024112705082867400_qiae207-B28","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1056\/nejm199010113231505","article-title":"Eosinophilic inflammation in asthma","volume":"323","author":"Bousquet","year":"1990","journal-title":"N Engl J Med"},{"issue":"129","key":"2024112705082867400_qiae207-B29","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1183\/09059180.00004013","article-title":"Anti-interleukin-5 therapy in severe asthma","volume":"22","author":"Garcia","year":"2013","journal-title":"Eur Respir Rev"},{"issue":"7","key":"2024112705082867400_qiae207-B30","doi-asserted-by":"publisher","first-page":"2394","DOI":"10.1172\/jci84144","article-title":"Current concepts of severe asthma","volume":"126","author":"Ray","year":"2016","journal-title":"J Clin Invest"},{"key":"2024112705082867400_qiae207-B31","author":"The Jackson Laboratory"},{"issue":"7","key":"2024112705082867400_qiae207-B32","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1182\/blood.V95.7.2284","article-title":"Expansion of hematopoietic stem cells in the developing liver of a mouse embryo","volume":"95","author":"Ema","year":"2000","journal-title":"Blood"},{"issue":"8","key":"2024112705082867400_qiae207-B33","doi-asserted-by":"publisher","first-page":"3689","DOI":"10.4049\/jimmunol.160.8.3689","article-title":"Phorbol esters induce differentiation of human CD34+ hemopoietic progenitors to dendritic cells: evidence for protein kinase C-mediated signaling","volume":"160","author":"Davis","year":"1998","journal-title":"J Immunol"},{"issue":"31","key":"2024112705082867400_qiae207-B34","doi-asserted-by":"publisher","first-page":"28412","DOI":"10.1074\/jbc.M500345200","article-title":"Protein kinase C betaII plays an essential role in dendritic cell differentiation and autoregulates its own expression","volume":"280","author":"Cejas","year":"2005","journal-title":"J Biol Chem"},{"issue":"1","key":"2024112705082867400_qiae207-B35","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/1471-2407-14-90","article-title":"Protein kinase C-\u03b4 inactivation inhibits the proliferation and survival of cancer stem cells in culture and in vivo","volume":"14","author":"Chen","year":"2014","journal-title":"BMC Cancer"},{"issue":"24","key":"2024112705082867400_qiae207-B36","doi-asserted-by":"publisher","first-page":"e100409","DOI":"10.15252\/embj.2018100409","article-title":"Attenuation of PKC\u03b4 enhances metabolic activity and promotes expansion of blood progenitors","volume":"37","author":"Rao","year":"2018","journal-title":"EMBO J"},{"issue":"3","key":"2024112705082867400_qiae207-B37","doi-asserted-by":"publisher","first-page":"1882","DOI":"10.4049\/jimmunol.178.3.1882","article-title":"Diverse and potent chemokine production by lung CD11bhigh dendritic cells in homeostasis and in allergic lung inflammation","volume":"178","author":"Beaty","year":"2007","journal-title":"J Immunol"},{"issue":"11","key":"2024112705082867400_qiae207-B38","doi-asserted-by":"publisher","first-page":"6861","DOI":"10.4049\/jimmunol.178.11.6861","article-title":"CD103- and CD103+ bronchial lymph node dendritic cells are specialized in presenting and cross-presenting innocuous antigen to CD4+ and CD8+ T cells","volume":"178","author":"del Rio","year":"2007","journal-title":"J Immunol"},{"issue":"2","key":"2024112705082867400_qiae207-B39","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/j.immuni.2012.10.016","article-title":"Conventional and monocyte-derived CD11b(+) dendritic cells initiate and maintain T helper 2 cell-mediated immunity to house dust mite allergen","volume":"38","author":"Plantinga","year":"2013","journal-title":"Immunity"},{"issue":"6","key":"2024112705082867400_qiae207-B40","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1093\/intimm\/dxm034","article-title":"Protein kinase C delta stimulates antigen presentation by class II MHC in murine dendritic cells","volume":"19","author":"Majewski","year":"2007","journal-title":"Int Immunol"},{"issue":"9","key":"2024112705082867400_qiae207-B41","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.tips.2007.07.003","article-title":"Rottlerin: an inappropriate and ineffective inhibitor of PKCdelta","volume":"28","author":"Soltoff","year":"2007","journal-title":"Trends Pharmacol Sci"},{"issue":"1","key":"2024112705082867400_qiae207-B42","doi-asserted-by":"publisher","first-page":"140","DOI":"10.2353\/ajpath.2007.060381","article-title":"Asbestos-induced peribronchiolar cell proliferation and cytokine production are attenuated in lungs of protein kinase C-delta knockout mice","volume":"170","author":"Shukla","year":"2007","journal-title":"Am J Pathol"},{"issue":"4","key":"2024112705082867400_qiae207-B43","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1165\/rcmb.2019-0214OC","article-title":"IL-5 exposure in utero increases lung nerve density and airway reactivity in adult offspring","volume":"62","author":"Lebold","year":"2020","journal-title":"Am J Respir Cell Mol Biol"}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jleukbio\/advance-article-pdf\/doi\/10.1093\/jleuko\/qiae207\/60064567\/qiae207.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/116\/6\/1432\/60829215\/qiae207.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/116\/6\/1432\/60829215\/qiae207.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T05:10:01Z","timestamp":1732684201000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/116\/6\/1432\/7766261"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,23]]},"references-count":43,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,9,23]]},"published-print":{"date-parts":[[2024,11,27]]}},"URL":"https:\/\/doi.org\/10.1093\/jleuko\/qiae207","relation":{},"ISSN":["1938-3673"],"issn-type":[{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,12]]},"published":{"date-parts":[[2024,9,23]]}}}