{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:15:15Z","timestamp":1791317715593,"version":"4.3.1"},"reference-count":89,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T00:00:00Z","timestamp":1701993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent and\/or chronic course of inflammatory skin lesions with intense pruritus. Its pathophysiologic features include barrier dysfunction, aberrant immune cell infiltration, and alterations in the microbiome that are associated with genetic and environmental factors. There is a complex crosstalk between these components, which is primarily mediated by cytokines. Epidermal barrier dysfunction is the hallmark of AD and is caused by the disruption of proteins and lipids responsible for establishing the skin barrier. To better define the role of cytokines in stratum corneum lipid abnormalities related to AD, we conducted a systematic review of biomedical literature in PubMed from its inception to 5 September 2023. Consistent with the dominant TH2 skewness seen in AD, type 2 cytokines were featured prominently as possessing a central role in epidermal lipid alterations in AD skin. The cytokines associated with TH1 and TH17 were also identified to affect barrier lipids. Considering the broad cytokine dysregulation observed in AD pathophysiology, understanding the role of each of these in lipid abnormalities and barrier dysfunction will help in developing therapeutics to best achieve barrier homeostasis in AD patients.<\/jats:p>","DOI":"10.3390\/cells12242793","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T05:47:30Z","timestamp":1702014450000},"page":"2793","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Cytokines and Epidermal Lipid Abnormalities in Atopic Dermatitis: A Systematic Review"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8691-617X","authenticated-orcid":false,"given":"Parth R.","family":"Upadhyay","sequence":"first","affiliation":[{"name":"Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6004-2451","authenticated-orcid":false,"given":"Lucia","family":"Seminario-Vidal","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Abe","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrus","family":"Ghobadi","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan T.","family":"Sims","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1111\/exd.13514","article-title":"Atopic dermatitis in diverse racial and ethnic groups-Variations in epidemiology, genetics, clinical presentation and treatment","volume":"27","author":"Kaufman","year":"2018","journal-title":"Exp. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.jaad.2018.09.035","article-title":"A systematic review and meta-analysis of the regional and age-related differences in atopic dermatitis clinical characteristics","volume":"80","author":"Yew","year":"2019","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.anai.2018.07.006","article-title":"Patient burden and quality of life in atopic dermatitis in US adults: A population-based cross-sectional study","volume":"121","author":"Silverberg","year":"2018","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jid.2016.07.012","article-title":"The Burden of Atopic Dermatitis: Summary of a Report for the National Eczema Association","volume":"137","author":"Drucker","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/s41423-023-00992-4","article-title":"The translational revolution in atopic dermatitis: The paradigm shift from pathogenesis to treatment","volume":"20","author":"Facheris","year":"2023","journal-title":"Cell Mol. Immunol."},{"key":"ref_6","first-page":"359","article-title":"Inside out or outside in: Does atopic dermatitis disrupt barrier function or does disruption of barrier function trigger atopic dermatitis?","volume":"96","author":"Silverberg","year":"2015","journal-title":"Cutis"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1111\/j.1600-0625.2008.00786.x","article-title":"The skin: An indispensable barrier","volume":"17","author":"Proksch","year":"2008","journal-title":"Exp. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/nrm1619","article-title":"The cornified envelope: A model of cell death in the skin","volume":"6","author":"Candi","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1056\/NEJMra2023911","article-title":"Atopic Dermatitis","volume":"384","author":"Stander","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1111\/j.1600-0625.2011.01259.x","article-title":"Distinct barrier integrity phenotypes in filaggrin-related atopic eczema following sequential tape stripping and lipid profiling","volume":"20","author":"Mannheimer","year":"2011","journal-title":"Exp. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.bbalip.2013.10.001","article-title":"Lipid abnormalities and lipid-based repair strategies in atopic dermatitis","volume":"1841","author":"Elias","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1194\/jlr.M800014-JLR200","article-title":"Characterization of overall ceramide species in human stratum corneum","volume":"49","author":"Masukawa","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1007\/s004030050344","article-title":"A new HPLC-based method for the quantitative analysis of inner stratum corneum lipids with special reference to the free fatty acid fraction","volume":"290","author":"Norlen","year":"1998","journal-title":"Arch. Dermatol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.bbalip.2013.11.007","article-title":"Role of lipids in the formation and maintenance of the cutaneous permeability barrier","volume":"1841","author":"Feingold","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"44s","DOI":"10.1038\/jid.1983.12","article-title":"Epidermal lipids, barrier function, and desquamation","volume":"80","author":"Elias","year":"1983","journal-title":"J. Investig. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/BF00371952","article-title":"Lipid composition of outer stratum corneum and nails in atopic and control subjects","volume":"282","author":"Melnik","year":"1990","journal-title":"Arch. Dermatol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/1523-1747.ep12470233","article-title":"Decreased level of ceramides in stratum corneum of atopic dermatitis: An etiologic factor in atopic dry skin?","volume":"96","author":"Imokawa","year":"1991","journal-title":"J. Investig. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/BF01106105","article-title":"Stratum corneum lipid abnormalities in atopic dermatitis","volume":"283","author":"Yamamoto","year":"1991","journal-title":"Arch. Dermatol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1038\/jid.2010.161","article-title":"Changes in the ceramide profile of atopic dermatitis patients","volume":"130","author":"Ishikawa","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15624","DOI":"10.1021\/la4037474","article-title":"Ceramides in the skin lipid membranes: Length matters","volume":"29","author":"Skolova","year":"2013","journal-title":"Langmuir"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1007\/BF02531977","article-title":"Fatty acid composition of the living layer and stratum corneum lipids of human sole skin epidermis","volume":"5","author":"Ansari","year":"1970","journal-title":"Lipids"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/exd.12293","article-title":"The importance of free fatty acid chain length for the skin barrier function in atopic eczema patients","volume":"23","author":"Janssens","year":"2014","journal-title":"Exp. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1016\/j.jaci.2018.02.040","article-title":"Early-onset pediatric atopic dermatitis is characterized by T(H)2\/T(H)17\/T(H)22-centered inflammation and lipid alterations","volume":"141","author":"Brunner","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"801579","DOI":"10.3389\/fimmu.2022.801579","article-title":"Cytokine-Mediated Crosstalk Between Keratinocytes and T Cells in Atopic Dermatitis","volume":"13","author":"Humeau","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"21895","DOI":"10.1038\/s41598-020-78943-6","article-title":"Cytokine concentration across the stratum corneum in atopic dermatitis and healthy controls","volume":"10","author":"Clausen","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"100131","DOI":"10.1016\/j.xjidi.2022.100131","article-title":"Type 2 Inflammation Contributes to Skin Barrier Dysfunction in Atopic Dermatitis","volume":"2","author":"Beck","year":"2022","journal-title":"JID Innov."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.jaci.2007.04.031","article-title":"Cytokine modulation of atopic dermatitis filaggrin skin expression","volume":"120","author":"Howell","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.clim.2007.11.006","article-title":"Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6","volume":"126","author":"Kim","year":"2008","journal-title":"Clin. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jaci.2018.08.022","article-title":"Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis","volume":"143","author":"Bissonnette","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jdermsci.2012.07.004","article-title":"Th1 cytokines accentuate but Th2 cytokines attenuate ceramide production in the stratum corneum of human epidermal equivalents: An implication for the disrupted barrier mechanism in atopic dermatitis","volume":"68","author":"Sawada","year":"2012","journal-title":"J. Dermatol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1038\/jid.2014.43","article-title":"Th2 cytokines increase Staphylococcus aureus alpha toxin-induced keratinocyte death through the signal transducer and activator of transcription 6 (STAT6)","volume":"134","author":"Brauweiler","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ewald, D.A., Malajian, D., Krueger, J.G., Workman, C.T., Wang, T., Tian, S., Litman, T., Guttman-Yassky, E., and Suarez-Farinas, M. (2015). Meta-analysis derived atopic dermatitis (MADAD) transcriptome defines a robust AD signature highlighting the involvement of atherosclerosis and lipid metabolism pathways. BMC Med. Genom., 8.","DOI":"10.1186\/s12920-015-0133-x"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jdermsci.2017.05.005","article-title":"Altered expression of epidermal lipid bio-synthesis enzymes in atopic dermatitis skin is accompanied by changes in stratum corneum lipid composition","volume":"88","author":"Danso","year":"2017","journal-title":"J. Dermatol. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Toncic, R.J., Jakasa, I., Hadzavdic, S.L., Goorden, S.M., Vlugt, K.J.G., Stet, F.S., Balic, A., Petkovic, M., Pavicic, B., and Zuzul, K. (2020). Altered Levels of Sphingosine, Sphinganine and Their Ceramides in Atopic Dermatitis Are Related to Skin Barrier Function, Disease Severity and Local Cytokine Milieu. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21061958"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e2100749118","DOI":"10.1073\/pnas.2100749118","article-title":"Interleukins 4 and 13 drive lipid abnormalities in skin cells through regulation of sex steroid hormone synthesis","volume":"118","author":"Zhang","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1111\/bjd.20979","article-title":"Children with atopic dermatitis show increased activity of beta-glucocerebrosidase and stratum corneum levels of glucosylcholesterol that are strongly related to the local cytokine milieu","volume":"186","author":"Kezic","year":"2022","journal-title":"Br. J. Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1111\/all.15640","article-title":"Staphylococcus aureus causes aberrant epidermal lipid composition and skin barrier dysfunction","volume":"78","author":"Kim","year":"2023","journal-title":"Allergy"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1111\/j.0022-202X.2005.23651.x","article-title":"Interleukin-4 suppresses the enhancement of ceramide synthesis and cutaneous permeability barrier functions induced by tumor necrosis factor-alpha and interferon-gamma in human epidermis","volume":"124","author":"Hatano","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jdermsci.2007.02.010","article-title":"Interleukin-4 depresses levels of transcripts for acid-sphingomyelinase and glucocerebrosidase and the amount of ceramide in acetone-wounded epidermis, as demonstrated in a living skin equivalent","volume":"47","author":"Hatano","year":"2007","journal-title":"J. Dermatol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e98006","DOI":"10.1172\/jci.insight.98006","article-title":"Lipid abnormalities in atopic skin are driven by type 2 cytokines","volume":"3","author":"Berdyshev","year":"2018","journal-title":"JCI Insight"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3388","DOI":"10.1111\/all.15432","article-title":"Dupilumab significantly improves skin barrier function in patients with moderate-to-severe atopic dermatitis","volume":"77","author":"Berdyshev","year":"2022","journal-title":"Allergy"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1111\/ced.12567","article-title":"The role of interleukin-17 in mouse models of atopic dermatitis and contact dermatitis","volume":"40","author":"Heo","year":"2015","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.jaci.2011.10.042","article-title":"IL-31 regulates differentiation and filaggrin expression in human organotypic skin models","volume":"129","author":"Cornelissen","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1111\/cea.12443","article-title":"Reduced filaggrin expression is accompanied by increased Staphylococcus aureus colonization of epidermal skin models","volume":"44","author":"Haisma","year":"2014","journal-title":"Clin. Exp. Allergy"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1038\/jid.2014.83","article-title":"TNF-alpha and Th2 cytokines induce atopic dermatitis-like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents","volume":"134","author":"Danso","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/jid.2013.364","article-title":"Interferon-gamma decreases ceramides with long-chain fatty acids: Possible involvement in atopic dermatitis and psoriasis","volume":"134","author":"Tawada","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3030268","DOI":"10.1155\/2019\/3030268","article-title":"IFN-gamma Reduces Epidermal Barrier Function by Affecting Fatty Acid Composition of Ceramide in a Mouse Atopic Dermatitis Model","volume":"2019","author":"Kanoh","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1016\/j.tiv.2009.07.021","article-title":"Microvesicating effects of sulfur mustard on an in vitro human skin model","volume":"23","author":"Hayden","year":"2009","journal-title":"Toxicol. In Vitro"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"830","DOI":"10.4049\/immunohorizons.2100055","article-title":"Transcriptomic Analysis of Healthy and Atopic Dermatitis Samples Reveals the Role of IL-37 in Human Skin","volume":"5","author":"Zhou","year":"2021","journal-title":"Immunohorizons"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Singh, B., Jegga, A.G., Shanmukhappa, K.S., Edukulla, R., Khurana Hershey, G.H., Medvedovic, M., Dillon, S.R., and Madala, S.K. (2016). IL-31-Driven Skin Remodeling Involves Epidermal Cell Proliferation and Thickening That Lead to Impaired Skin-Barrier Function. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161877"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"17180","DOI":"10.1016\/S0021-9258(17)44886-1","article-title":"A novel transglutaminase-mediated post-translational modification of phospholipase A2 dramatically increases its catalytic activity","volume":"265","author":"Miele","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"38104","DOI":"10.1074\/jbc.M005296200","article-title":"Posttranslational regulation of acid sphingomyelinase in niemann-pick type C1 fibroblasts and free cholesterol-enriched chinese hamster ovary cells","volume":"275","author":"Reagan","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.bbrc.2009.02.063","article-title":"Sphingomyelin synthase 2 is palmitoylated at the COOH-terminal tail, which is involved in its localization in plasma membranes","volume":"381","author":"Tani","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.jaci.2015.04.026","article-title":"Thymic stromal lymphopoietin downregulates filaggrin expression by signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) phosphorylation in keratinocytes","volume":"136","author":"Kim","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3186","DOI":"10.4049\/jimmunol.0901860","article-title":"IL-4 regulates skin homeostasis and the predisposition toward allergic skin inflammation","volume":"184","author":"Sehra","year":"2010","journal-title":"J. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1016\/j.jaci.2015.01.048","article-title":"IL-33 impacts on the skin barrier by downregulating the expression of filaggrin","volume":"135","author":"Seltmann","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/j.jaci.2009.09.031","article-title":"Broad defects in epidermal cornification in atopic dermatitis identified through genomic analysis","volume":"124","author":"Chiricozzi","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.anai.2018.11.015","article-title":"Racial differences in atopic dermatitis","volume":"122","author":"Brunner","year":"2019","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1038\/jid.2008.111","article-title":"Possible pathogenic role of Th17 cells for atopic dermatitis","volume":"128","author":"Koga","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Sugaya, M. (2020). The Role of Th17-Related Cytokines in Atopic Dermatitis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041314"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.5114\/ada.2022.122604","article-title":"The role of heterodimer IL-17-A\/F in atopic dermatitis","volume":"39","author":"Krzysiek","year":"2022","journal-title":"Postepy Dermatol. Alergol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1600-0625.2011.01412.x","article-title":"IL-17 downregulates filaggrin and affects keratinocyte expression of genes associated with cellular adhesion","volume":"21","author":"Schaupp","year":"2012","journal-title":"Exp. Dermatol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Furue, M. (2020). Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155382"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"8863","DOI":"10.3892\/mmr.2017.7689","article-title":"P38\/ERK MAPK signaling pathways are involved in the regulation of filaggrin and involucrin by IL-17","volume":"16","author":"Tan","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1038\/jid.2014.51","article-title":"IL-17A as an inducer for Th2 immune responses in murine atopic dermatitis models","volume":"134","author":"Nakajima","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1016\/j.jid.2018.01.036","article-title":"Neutralization of IL-17C Reduces Skin Inflammation in Mouse Models of Psoriasis and Atopic Dermatitis","volume":"138","author":"Vandeghinste","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41572-018-0001-z","article-title":"Atopic dermatitis","volume":"4","author":"Weidinger","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jdermsci.2012.04.004","article-title":"A group of atopic dermatitis without IgE elevation or barrier impairment shows a high Th1 frequency: Possible immunological state of the intrinsic type","volume":"67","author":"Nakamura","year":"2012","journal-title":"J. Dermatol. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1038\/s41590-021-01009-w","article-title":"Repositioning T(H) cell polarization from single cytokines to complex help","volume":"22","author":"Tuzlak","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.clim.2016.11.001","article-title":"Allergies\u2014A T cells perspective in the era beyond the T(H)1\/T(H)2 paradigm","volume":"174","author":"Berker","year":"2017","journal-title":"Clin. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1172\/JCI119496","article-title":"Granulocyte macrophage colony-stimulating factor is overproduced by keratinocytes in atopic dermatitis. Implications for sustained dendritic cell activation in the skin","volume":"99","author":"Pastore","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1007\/s11882-004-0071-8","article-title":"Keratinocytes in atopic dermatitis: Inflammatory signals","volume":"4","author":"Esche","year":"2004","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1067\/mjd.2002.124617","article-title":"Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis: Changes in barrier function provide a sensitive indicator of disease activity","volume":"47","author":"Chamlin","year":"2002","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3109\/09546630903085336","article-title":"A new moisturizer containing physiologic lipid granules alleviates atopic dermatitis","volume":"21","author":"Na","year":"2010","journal-title":"J. Dermatol. Treat."},{"key":"ref_75","first-page":"34","article-title":"Evaluating Clinical Use of a Ceramide-dominant, Physiologic Lipid-based Topical Emulsion for Atopic Dermatitis","volume":"4","author":"Kircik","year":"2011","journal-title":"J. Clin. Aesthet. Dermatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1034\/j.1600-0536.2001.450505.x","article-title":"Evaluation of efficacy of a skin lipid mixture in patients with irritant contact dermatitis, allergic contact dermatitis or atopic dermatitis: A multicenter study","volume":"45","author":"Berardesca","year":"2001","journal-title":"Contact Dermat."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1016\/j.intimp.2007.08.009","article-title":"Topical application of a novel ceramide derivative, K6PC-9, inhibits dust mite extract-induced atopic dermatitis-like skin lesions in NC\/Nga mice","volume":"7","author":"Kang","year":"2007","journal-title":"Int. Immunopharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1111\/j.1600-0625.2008.00737.x","article-title":"Inhibition of atopic dermatitis-like skin lesions by topical application of a novel ceramide derivative, K6PC-9p, in NC\/Nga mice","volume":"17","author":"Kang","year":"2008","journal-title":"Exp. Dermatol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1111\/exd.14806","article-title":"Topical emollient prevents the development of atopic dermatitis and atopic march in mice","volume":"32","author":"Zhang","year":"2023","journal-title":"Exp. Dermatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1159\/000448400","article-title":"Stratum Corneum Tape Stripping: Monitoring of Inflammatory Mediators in Atopic Dermatitis Patients Using Topical Therapy","volume":"170","author":"Koppes","year":"2016","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"766","DOI":"10.3346\/jkms.2010.25.5.766","article-title":"Changes of antimicrobial peptides and transepidermal water loss after topical application of tacrolimus and ceramide-dominant emollient in patients with atopic dermatitis","volume":"25","author":"Park","year":"2010","journal-title":"J. Korean Med. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s40257-018-0413-2","article-title":"JAK Inhibitors for Atopic Dermatitis: An Update","volume":"20","author":"He","year":"2019","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_83","unstructured":"(2023, October 03). ANNEX I\u2014Summary of Product Characteristics. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/adtralza-epar-product-information_en.pdf."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.jaad.2018.01.016","article-title":"Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: A randomized, double-blind, phase 2a trial","volume":"78","author":"Brunner","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/jid.2013.402","article-title":"Filaggrin deficiency leads to impaired lipid profile and altered acidification pathways in a 3D skin construct","volume":"134","author":"Vavrova","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1111\/exd.12271","article-title":"Knock-down of filaggrin does not affect lipid organization and composition in stratum corneum of reconstructed human skin equivalents","volume":"22","author":"Danso","year":"2013","journal-title":"Exp. Dermatol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1111\/all.15518","article-title":"Skin biomarkers predict development of atopic dermatitis in infancy","volume":"78","author":"Rinnov","year":"2023","journal-title":"Allergy"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/j.jaci.2023.02.013","article-title":"Stratum corneum lipid and cytokine biomarkers at age 2 months predict the future onset of atopic dermatitis","volume":"151","author":"Berdyshev","year":"2023","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.molmed.2019.04.001","article-title":"Epidermal Lipids: Key Mediators of Atopic Dermatitis Pathogenesis","volume":"25","author":"Bhattacharya","year":"2019","journal-title":"Trends Mol. Med."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/24\/2793\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:35:18Z","timestamp":1760132118000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/24\/2793"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,8]]},"references-count":89,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["cells12242793"],"URL":"https:\/\/doi.org\/10.3390\/cells12242793","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,8]]}}}