{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T04:29:51Z","timestamp":1789273791937,"version":"build-2803163510"},"reference-count":117,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"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), characterized by rashes, itching, and pruritus, is a chronic inflammatory condition of the skin with a marked infiltration of inflammatory cells into the lesion. It usually commences in early childhood and coexists with other atopic diseases such as allergic rhinitis, bronchial asthma, allergic conjunctivitis, etc. With a prevalence rate of 1\u201320% in adults and children worldwide, AD is gradually becoming a major health concern. Immunological aspects have been frequently focused on in the pathogenesis of AD, including the role of the epidermal barrier and the consequent abnormal cytokine expressions. Disrupted epidermal barriers, as well as allergic triggers (food allergy), contact allergens, irritants, microbes, aggravating factors, and ultraviolet light directly initiate the inflammatory response by inducing epidermal keratinocytes, resulting in the abnormal release of various pro-inflammatory mediators, inflammatory cytokines, and chemokines from keratinocytes. In addition, abnormal proteinases, gene mutations, or single nucleotide polymorphisms (SNP) affecting the function of the epidermal barrier can also contribute towards disease pathophysiology. Apart from this, imbalances in cholinergic or adrenergic responses in the epidermis or the role played by immune cells in the epidermis such as Langerhans cells or antigen-presenting cells can also aggravate pathophysiology. The dearth of specific biomarkers for proper diagnosis and the lack of a permanent cure for AD necessitate investigation in this area. In this context, the widespread role played by keratinocytes in the pathogenesis of AD will be reviewed in this article to facilitate the opening up of new avenues of treatment for AD.<\/jats:p>","DOI":"10.3390\/cells11101683","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T12:25:57Z","timestamp":1652963157000},"page":"1683","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Keratinocytes: An Enigmatic Factor in Atopic Dermatitis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4260-9012","authenticated-orcid":false,"given":"Pamelika","family":"Das","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Kolkata, Chunilal Bhawan, 168 Maniktala Main Road, Kolkata 700054, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pappula","family":"Mounika","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Kolkata, Chunilal Bhawan, 168 Maniktala Main Road, Kolkata 700054, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoj Limbraj","family":"Yellurkar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Kolkata, Chunilal Bhawan, 168 Maniktala Main Road, Kolkata 700054, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vani Sai","family":"Prasanna","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Kolkata, Chunilal Bhawan, 168 Maniktala Main Road, Kolkata 700054, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sulogna","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Kolkata, Chunilal Bhawan, 168 Maniktala Main Road, Kolkata 700054, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravichandiran","family":"Velayutham","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Kolkata, Chunilal Bhawan, 168 Maniktala Main Road, Kolkata 700054, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2096-2552","authenticated-orcid":false,"given":"Somasundaram","family":"Arumugam","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Kolkata, Chunilal Bhawan, 168 Maniktala Main Road, Kolkata 700054, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/0140-6736(91)92168-2","article-title":"Keratinocytes as Initiators of Inflammation","volume":"337","author":"Barker","year":"1991","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/cei.13575","article-title":"Keratinocytes: Innate Immune Cells in Atopic Dermatitis","volume":"204","author":"Chieosilapatham","year":"2021","journal-title":"Clin. Exp. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.jaad.2003.09.010","article-title":"Innate Immune Defense of the Nail Unit by Antimicrobial Peptides","volume":"50","author":"Dorschner","year":"2004","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1067\/mjd.2001.117021","article-title":"The Role of Keratinocytes in the Pathogenesis of Atopic Dermatitis","volume":"45","author":"Girolomoni","year":"2001","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1038\/jid.2009.71","article-title":"The Role of Leukocytes, Keratinocytes, and Allergen-Specific IgE in the Development of Atopic Dermatitis","volume":"129","author":"Werfel","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/sj.jid.5700085","article-title":"IL-13-Stimulated Human Keratinocytes Preferentially Attract CD4+ CCR4+ T Cells: Possible Role in Atopic Dermatitis","volume":"126","author":"Purwar","year":"2006","journal-title":"J. Investig. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"329","DOI":"10.2174\/1568010054022033","article-title":"Keratinocytes in Inflammatory Skin Diseases","volume":"4","author":"Albanesi","year":"2005","journal-title":"Curr. Drug Targets Inflamm. Allergy"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1046\/j.1523-1747.2000.00115.x","article-title":"A Th2 Chemokine, TARC, Produced by Keratinocytes May Recruit CLA+CCR4+ Lymphocytes into Lesional Atopic Dermatitis Skin","volume":"115","author":"Vestergaard","year":"2000","journal-title":"J. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1254\/jphs.09R06FM","article-title":"Analysis of the Mechanism for the Development of Allergic Skin Inflammation and the Application for Its Treatment: Keratinocytes in Atopic Dermatitis\u2014Their Pathogenic Involvement","volume":"110","author":"Komine","year":"2009","journal-title":"J. Pharmacol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.jid.2019.07.713","article-title":"Increased IL-26 Expression Promotes T Helper Type 17- and T Helper Type 2-Associated Cytokine Production by Keratinocytes in Atopic Dermatitis","volume":"140","author":"Kamijo","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"17679","DOI":"10.1038\/s41598-017-17873-2","article-title":"Beneficial Effects of Melittin on Ovalbumin-Induced Atopic Dermatitis in Mouse","volume":"7","author":"Kim","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1016\/S0024-3205(03)00079-1","article-title":"Increased Acetylcholine Levels in Skin Biopsies of Patients with Atopic Dermatitis","volume":"72","author":"Wessler","year":"2003","journal-title":"Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/j.jaci.2017.01.039","article-title":"Proteomic Analysis of Filaggrin Deficiency Identifies Molecular Signatures Characteristic of Atopic Eczema","volume":"140","author":"Elias","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1111\/1523-1747.ep12320329","article-title":"Interleukin-1 Receptor Antagonist Suppresses Contact Hypersensitivity","volume":"105","author":"Kondo","year":"1995","journal-title":"J. Investig. Dermatol."},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1046\/j.1523-1747.2001.01327.x","article-title":"Keratins and the Keratinocyte Activation Cycle","volume":"116","author":"Freedberg","year":"2001","journal-title":"J. Investig. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0065-2776(08)60642-2","article-title":"Interleukin-1 and Its Biologically Related Cytokines","volume":"44","author":"Dinarello","year":"1989","journal-title":"Adv. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0165-2427(02)00136-8","article-title":"Keratinocytes and Cytokines","volume":"88","year":"2002","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.4049\/jimmunol.165.3.1395","article-title":"IL-4 Enhances Keratinocyte Expression of CXCR3 Agonistic Chemokines","volume":"165","author":"Albanesi","year":"2000","journal-title":"J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1002\/JLB.2MR0220-549R","article-title":"ICAM-1: A Master Regulator of Cellular Responses in Inflammation, Injury Resolution, and Tumorigenesis","volume":"108","author":"Bui","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1172\/JCI114481","article-title":"Marked Synergism between Tumor Necrosis Factor-\u03b1 and Interferon-\u03b3 in Regulation of Keratinocyte-Derived Adhesion Molecules and Chemotactic Factors","volume":"85","author":"Barker","year":"1990","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1093\/intimm\/13.1.95","article-title":"Inducible Expression of a CC Chemokine Liver- and Activation-Regulated Chemokine (LARC)\/Macrophage Inflammatory Protein (MIP)-3\u03b1\/CCL20 by Epidermal Keratinocytes and Its Role in Atopic Dermatitis","volume":"13","author":"Nakayama","year":"2001","journal-title":"Int. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1097\/01.all.0000244792.95615.3a","article-title":"Interaction of Keratinocytes with Infiltrating Lymphocytes in Allergic Eczematous Skin Diseases","volume":"6","author":"Wittmann","year":"2006","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"718725","DOI":"10.1155\/2012\/718725","article-title":"Keratinocytes under Fire of Proinflammatory Cytokines: Bona Fide Innate Immune Cells Involved in the Physiopathology of Chronic Atopic Dermatitis and Psoriasis","volume":"2012","author":"Bernard","year":"2012","journal-title":"J. Allergy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1084\/jem.192.5.705","article-title":"Macrophage Inflammatory Protein 3\u03b1 Is Expressed at Inflamed Epithelial Surfaces and Is the Most Potent Chemokine Known in Attracting Langerhans Cell Precursors","volume":"192","author":"Massacrier","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1111\/all.12529","article-title":"Update on Skin Allergy","volume":"69","author":"Schlapbach","year":"2014","journal-title":"Allergy Eur. J. Allergy Clin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1067\/mai.2003.155","article-title":"Advances in Allergic Skin Diseases","volume":"111","author":"Leung","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1097\/ACI.0b013e32833e08ae","article-title":"Keratinocytes in Allergic Skin Diseases","volume":"10","author":"Albanesi","year":"2010","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1097\/00130832-200410000-00009","article-title":"Role of Food Allergy in Atopic Dermatitis","volume":"4","author":"Werfel","year":"2004","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s40248-019-0199-y","article-title":"Sensitization to Inhaled Allergens in Asthmatic Children in Southern Jordan: A Cross-Sectional Study","volume":"14","author":"Alnawaiseh","year":"2019","journal-title":"Multidiscip. Respir. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1177\/12034754990030S205","article-title":"The Role of Food and Inhaled Allergens in Atopic Dermatitis","volume":"3","author":"Grunebaum","year":"1999","journal-title":"J. Cutan. Med. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/jid.1949.33","article-title":"Importance of Inhalant Allergens in Atopic Dermatitis","volume":"12","author":"TUFT","year":"1949","journal-title":"J. Investig. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Erwin, E.A., Woodfolk, J.A., and Platts-Mills, T.A.E. (2006). The Role of Inhalant Allergens in Atopic Dermatitis. Handbook of Atopic Eczema, Springer.","DOI":"10.1007\/3-540-29856-8_40"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Mrabet-Dahbi, S., and Renz, H. (2008). Role of Inhalant Allergens in Atopic Dermatitis. Textbook of Atopic Dermatitis, Informa Healthcare.","DOI":"10.3109\/9780203091449.009"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Chiu, C.Y., Huang, Y.L., Tsai, M.H., Tu, Y.L., Hua, M.C., Yao, T.C., Yeh, K.W., and Huang, J.L. (2014). Sensitization to Food and Inhalant Allergens in Relation to Atopic Diseases in Early Childhood: A Birth Cohort Study. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102809"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1089\/wound.2013.0473","article-title":"Epithelialization in Wound Healing: A Comprehensive Review","volume":"3","author":"Pastar","year":"2014","journal-title":"Adv. Wound Care"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Piipponen, M., Li, D., and Land\u00e9n, N.X. (2020). The Immune Functions of Keratinocytes in Skin Wound Healing. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228790"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.clindermatol.2006.09.007","article-title":"Pathophysiology of Acute Wound Healing","volume":"25","author":"Li","year":"2007","journal-title":"Clin. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.dsi.2014.05.002","article-title":"Keratinocytes Regulate the Function of Melanocytes","volume":"32","author":"Hirobe","year":"2014","journal-title":"Dermatol. Sin."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1093\/intimm\/dxg068","article-title":"Expression and Function of Toll-like Receptors 2 and 4 in Human Keratinocytes","volume":"15","author":"Pivarcsi","year":"2003","journal-title":"Int. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00281-007-0061-8","article-title":"Toll-like Receptors in the Skin","volume":"29","author":"Miller","year":"2007","journal-title":"Semin. Immunopathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1016\/j.jaci.2018.11.036","article-title":"A Tryptophan Metabolite of the Skin Microbiota Attenuates Inflammation in Patients with Atopic Dermatitis through the Aryl Hydrocarbon Receptor","volume":"143","author":"Yu","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_44","first-page":"917","article-title":"Coal Tar Induces AHR-Dependent Skin Barrier Repair in Atopic Dermatitis","volume":"123","author":"Bergboer","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/jid.2011.387","article-title":"Antimicrobial Peptides: Old Molecules with New Ideas","volume":"132","author":"Nakatsuji","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.immuni.2006.02.006","article-title":"Cytokine Milieu of Atopic Dermatitis Skin Subverts the Innate Immune Response to Vaccinia Virus","volume":"24","author":"Howell","year":"2006","journal-title":"Immunity"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1038\/jid.2014.143","article-title":"Host Defense (Antimicrobial) Peptide, Human \u03b2-Defensin-3, Improves the Function of the Epithelial Tight-Junction Barrier in Human Keratinocytes","volume":"134","author":"Kiatsurayanon","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.4049\/jimmunol.175.3.1776","article-title":"The Human \u03b2-Defensins (-1, -2, -3, -4) and Cathelicidin LL-37 Induce IL-18 Secretion through P38 and ERK MAPK Activation in Primary Human Keratinocytes","volume":"175","author":"Niyonsaba","year":"2005","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/sj.jid.5700599","article-title":"Antimicrobial Peptides Human \u03b2-Defensins Stimulate Epidermal Keratinocyte Migration, Proliferation and Production of Proinflammatory Cytokines and Chemokines","volume":"127","author":"Niyonsaba","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.imlet.2018.06.009","article-title":"Taking the Lead\u2014How Keratinocytes Orchestrate Skin T Cell Immunity","volume":"200","author":"Klicznik","year":"2018","journal-title":"Immunol. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e142067","DOI":"10.1172\/jci.insight.142067","article-title":"Cytokinocytes: The Diverse Contribution of Keratinocytes to Immune Responses in Skin","volume":"5","author":"Jiang","year":"2020","journal-title":"JCI Insight"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1016\/j.jid.2018.08.004","article-title":"NLRP1 Is the Key Inflammasome in Primary Human Keratinocytes","volume":"138","author":"Burian","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1038\/jid.2008.395","article-title":"Functional Expression of the Intracellular Pattern Recognition Receptor NOD1 in Human Keratinocytes","volume":"129","author":"Harder","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.jaci.2010.12.006","article-title":"Mite Allergen Is a Danger Signal for the Skin via Activation of Inflammasome in Keratinocytes","volume":"127","author":"Dai","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.bbrc.2016.06.106","article-title":"Nuclear DNA Damage-Triggered NLRP3 Inflammasome Activation Promotes UVB-Induced Inflammatory Responses in Human Keratinocytes","volume":"477","author":"Hasegawa","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/j.1365-2567.2005.02122.x","article-title":"Various Members of the Toll-like Receptor Family Contribute to the Innate Immune Response of Human Epidermal Keratinocytes","volume":"114","author":"Kalali","year":"2005","journal-title":"Immunology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1111\/j.1523-1747.2003.12630.x","article-title":"Toll-like Receptor Expression in Human Keratinocytes: Nuclear Factor \u039aB Controlled Gene Activation by Staphylococcus Aureus Is Toll-like Receptor 2 but Not Toll-like Receptor 4 or Platelet Activating Factor Receptor Dependent","volume":"121","author":"Mempel","year":"2003","journal-title":"J. Investig. Dermatol."},{"key":"ref_58","first-page":"432785","article-title":"Collaborative Action of Toll-like and Nod-like Receptors as Modulators of the Inflammatory Response to Pathogenic Bacteria","volume":"2014","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1111\/j.1462-5822.2009.01285.x","article-title":"Innate Immune Responses to Mycobacterium Ulcerans via Toll-like Receptors and Dectin-1 in Human Keratinocytes","volume":"11","author":"Lee","year":"2009","journal-title":"Cell. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cellimm.2014.03.007","article-title":"Dectin-1 Activation Induces Proliferation and Migration of Human Keratinocytes Enhancing Wound Re-Epithelialization","volume":"289","author":"Richters","year":"2014","journal-title":"Cell. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.4049\/jimmunol.181.4.2694","article-title":"Double-Stranded RNA Induces an Antiviral Defense Status in Epidermal Keratinocytes through TLR3-, PKR-, and MDA5\/RIG-I-Mediated Differential Signaling","volume":"181","author":"Kalali","year":"2008","journal-title":"J. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1093\/intimm\/dxp017","article-title":"The Roles of TLRs, RLRs and NLRs in Pathogen Recognition","volume":"21","author":"Kawai","year":"2009","journal-title":"Int. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1002\/eji.200636915","article-title":"Human Keratinocyte Induction of Rapid Effector Function in Antigen-Specific Memory CD4+ and CD8+ T Cells","volume":"37","author":"Black","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"23643","DOI":"10.1073\/pnas.1912432116","article-title":"Keratinocyte-Intrinsic MHCII Expression Controls Microbiota-Induced Th1 Cell Responses","volume":"116","author":"Tamoutounour","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/intimm\/dxz067","article-title":"DOCK Family Proteins: Key Players in Immune Surveillance Mechanisms","volume":"32","author":"Kunimura","year":"2020","journal-title":"Int. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1038\/s41591-018-0211-7","article-title":"Expanded Skin Virome in DOCK8-Deficient Patients","volume":"24","author":"Tirosh","year":"2018","journal-title":"Nat. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5156","DOI":"10.1038\/s41598-019-41480-y","article-title":"Effect of Mechanical Stretch on the DNCB-Induced Proinflammatory Cytokine Secretion in Human Keratinocytes","volume":"9","author":"Oh","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1111\/j.0022-202X.2004.22328.x","article-title":"Mechanical Stretching in Vitro Regulates Signal Transduction Pathways and Cellular Proliferation in Human Epidermal Keratinocytes","volume":"122","author":"Yano","year":"2004","journal-title":"J. Investig. Dermatol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1172\/JCI117408","article-title":"Differential in Situ Cytokine Gene Expression in Acute versus Chronic Atopic Dermatitis","volume":"94","author":"Hamid","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"84","DOI":"10.2500\/aap.2019.40.4202","article-title":"Pathophysiology of Atopic Dermatitis: Clinical Implications","volume":"40","author":"Kim","year":"2019","journal-title":"Allergy Asthma Proc."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/nature25465","article-title":"Asparagine Bioavailability Governs Metastasis in a Model of Breast Cancer","volume":"554","author":"Knott","year":"2018","journal-title":"Nature"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/exd.13336","article-title":"Systemic Immune Mechanisms in Atopic Dermatitis and Psoriasis with Implications for Treatment","volume":"27","author":"Krueger","year":"2018","journal-title":"Exp. Dermatol."},{"key":"ref_73","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_74","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.1038\/jid.2008.74","article-title":"Th2 Cytokines Act on S100\/A11 to Downregulate Keratinocyte Differentiation","volume":"128","author":"Howell","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1007\/s11882-996-0008-5","article-title":"Immune Dysregulation in Atopic Dermatitis","volume":"6","author":"Ong","year":"2006","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/0030-4220(85)90105-7","article-title":"Blood Loss Following Dental Extractions in Anticoagulated Rabbits: Effects of Tranexamic Acid and Socket Packing","volume":"59","author":"Vinckier","year":"1985","journal-title":"Oral Surg. Oral Med. Oral Pathol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1172\/JCI5669","article-title":"Roles of T(H)1 and T(H)2 Cytokines in a Murine Model of Allergic Dermatitis","volume":"103","author":"Spergel","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5571","DOI":"10.4049\/jimmunol.178.9.5571","article-title":"Skin-Infiltrating CD8 + T Cells Initiate Atopic Dermatitis Lesions","volume":"178","author":"Hennino","year":"2007","journal-title":"J. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/j.1365-2249.2004.02649.x","article-title":"Early Up-Regulation of Th2 Cytokines and Late Surge of Th1 Cytokines in an Atopic Dermatitis Model","volume":"138","author":"Chen","year":"2004","journal-title":"Clin. Exp. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1111\/j.1398-9995.2009.01947.x","article-title":"Early Production of Thymic Stromal Lymphopoietin Precedes Infiltration of Dendritic Cells Expressing Its Receptor in Allergen-Induced Late Phase Cutaneous Responses in Atopic Subjects","volume":"64","author":"Corrigan","year":"2009","journal-title":"Allergy Eur. J. Allergy Clin. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.4049\/jimmunol.178.6.3373","article-title":"Cutting Edge: Proinflammatory and Th2 Cytokines Synergize to Induce Thymic Stromal Lymphopoietin Production by Human Skin Keratinocytes","volume":"178","author":"Bogiatzi","year":"2007","journal-title":"J. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1016\/j.jaci.2012.07.012","article-title":"Progressive Activation of TH2\/TH22 Cytokines and Selective Epidermal Proteins Characterizes Acute and Chronic Atopic Dermatitis","volume":"130","author":"Gittler","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_83","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_84","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1111\/j.1398-9995.2009.02255.x","article-title":"Interleukin (IL)-31 Induces pro-Inflammatory Cytokines in Human Monocytes and Macrophages Following Stimulation with Staphylococcal Exotoxins","volume":"65","author":"Kasraie","year":"2010","journal-title":"Allergy Eur. J. Allergy Clin. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"eaal4651","DOI":"10.1126\/scitranslmed.aal4651","article-title":"Staphylococcus aureus and Staphylococcus epidermidisstrain diversity underlying pediatric atopic dermatitis","volume":"9","author":"Byrd","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2332\/allergolint.13-RAI-0564","article-title":"New Insights into Atopic Dermatitis: Role of Skin Barrier and Immune Dysregulation","volume":"62","author":"Leung","year":"2013","journal-title":"Allergol. Int."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1056\/NEJMoa021481","article-title":"Endogenous Antimicrobial Peptides and Skin Infections in Atopic Dermatitis","volume":"347","author":"Ong","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"261","DOI":"10.2165\/00128071-200203040-00004","article-title":"The Acidic Milieu of the Horny Layer","volume":"3","author":"Rippke","year":"2002","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.jid.2015.12.006","article-title":"Interferon-\u03b3 Protects from Staphylococcal Alpha Toxin-Induced Keratinocyte Death through Apolipoprotein L1","volume":"136","author":"Brauweiler","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e125","DOI":"10.1111\/bjd.15409","article-title":"Altered Composition of Epidermal Lipids Correlates with Staphylococcus Aureus Colonization Status in Atopic Dermatitis","volume":"177","author":"Li","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_91","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_92","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s00403-016-1674-3","article-title":"A Synthetic C16 Omega-Hydroxyphytoceramide Improves Skin Barrier Functions from Diversely Perturbed Epidermal Conditions","volume":"308","author":"Oh","year":"2016","journal-title":"Arch. Dermatol. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.1111\/bjd.15747","article-title":"A Randomized Trial of a Barrier Lipid Replacement Strategy for the Prevention of Atopic Dermatitis and Allergic Sensitization: The PEBBLES Pilot Study","volume":"178","author":"Lowe","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41573-021-00266-6","article-title":"Atopic Dermatitis: An Expanding Therapeutic Pipeline for a Complex Disease","volume":"21","author":"Bieber","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2572","DOI":"10.1038\/jid.2015.285","article-title":"The Janus-Faced Role of Aryl Hydrocarbon Receptor Signaling in the Skin: Consequences for Prevention and Treatment of Skin Disorders","volume":"135","author":"Esser","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1016\/j.jid.2017.05.004","article-title":"Tapinarof Is a Natural AhR Agonist That Resolves Skin Inflammation in Mice and Humans","volume":"137","author":"Smith","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.jaad.2020.05.135","article-title":"Efficacy and Patient-Reported Outcomes from a Phase 2b, Randomized Clinical Trial of Tapinarof Cream for the Treatment of Adolescents and Adults with Atopic Dermatitis","volume":"84","author":"Paller","year":"2021","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.jaad.2018.11.059","article-title":"Tezepelumab, an Anti\u2013Thymic Stromal Lymphopoietin Monoclonal Antibody, in the Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Phase 2a Clinical Trial","volume":"80","author":"Simpson","year":"2019","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1186\/s12931-020-01541-7","article-title":"DESTINATION: A Phase 3, Multicentre, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial to Evaluate the Long-Term Safety and Tolerability of Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma","volume":"21","author":"Ponnarambil","year":"2020","journal-title":"Respir. Res."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Pelaia, C., Pelaia, G., Longhini, F., Crimi, C., Calabrese, C., Gallelli, L., Sciacqua, A., and Vatrella, A. (2021). Monoclonal Antibodies Targeting Alarmins: A New Perspective for Biological Therapies of Severe Asthma. Biomedicines, 9.","DOI":"10.3390\/biomedicines9091108"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"eaax2945","DOI":"10.1126\/scitranslmed.aax2945","article-title":"Proof-of-Concept Clinical Trial of Etokimab Shows a Key Role for IL-33 in Atopic Dermatitis Pathogenesis","volume":"11","author":"Chen","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1016\/j.jaci.2018.08.042","article-title":"Injury, Dysbiosis, and Filaggrin Deficiency Drive Skin Inflammation through Keratinocyte IL-1\u03b1 Release","volume":"143","author":"Archer","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1551651","DOI":"10.1080\/2162402X.2018.1551651","article-title":"Interleukin-1 Receptor Antagonist Levels Predict Favorable Outcome after Bermekimab, a First-in-Class True Human Interleukin-1\u03b1 Antibody, in a Phase III Randomized Study of Advanced Colorectal Cancer","volume":"8","author":"Kurzrock","year":"2019","journal-title":"Oncoimmunology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.chom.2017.10.006","article-title":"Staphylococcus Aureus Epicutaneous Exposure Drives Skin Inflammation via IL-36-Mediated T Cell Responses","volume":"22","author":"Liu","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1056\/NEJMoa2111563","article-title":"Trial of Spesolimab for Generalized Pustular Psoriasis","volume":"385","author":"Bachelez","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"23","DOI":"10.2147\/DDDT.S326332","article-title":"Promising Natural Products in New Drug Design, Development, and Therapy for Skin Disorders: An Overview of Scientific Evidence and Understanding Their Mechanism of Action","volume":"16","author":"Sekar","year":"2022","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.intimp.2017.02.014","article-title":"Mangiferin Antagonizes TNF-\u03b1-Mediated Inflammatory Reaction and Protects against Dermatitis in a Mice Model","volume":"45","author":"Zhao","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1089\/acm.2008.0508","article-title":"Clinical Evaluation of an Indian Polyherbal Topical Formulation in the Management of Eczema","volume":"15","author":"Rawal","year":"2009","journal-title":"J. Altern. Complement. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.lfs.2013.07.027","article-title":"The Inhibitory Effect of Naringenin on Atopic Dermatitis Induced by DNFB in NC\/Nga Mice","volume":"93","author":"Kim","year":"2013","journal-title":"Life Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.ijbiomac.2020.07.168","article-title":"Cellulose Microsponges Based Gel of Naringenin for Atopic Dermatitis: Design, Optimization, in Vitro and in Vivo Investigation","volume":"164","author":"Nagula","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Weng, Z., Zhang, B., Asadi, S., Sismanopoulos, N., and Butcher, A. (2012). Quercetin Is More Effective than Cromolyn in Blocking Human Mast Cell Cytokine Release and Inhibits Contact Dermatitis and Photosensitivity in Humans. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033805"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1038\/jid.2009.401","article-title":"Tannic Acid and Quercetin Display a Therapeutic Effect in Atopic Dermatitis via Suppression of Angiogenesis and TARC Expression in Nc\/Nga Mice","volume":"130","author":"Jung","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"912028","DOI":"10.1155\/2012\/912028","article-title":"Topical Apigenin Alleviates Cutaneous Inflammation in Murine Models","volume":"2012","author":"Man","year":"2012","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/j.jaci.2014.08.005","article-title":"Emollient Enhancement of the Skin Barrier from Birth Offers Effective Atopic Dermatitis Prevention","volume":"134","author":"Simpson","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.jaci.2014.07.060","article-title":"Application of Moisturizer to Neonates Prevents Development of Atopic Dermatitis","volume":"134","author":"Horimukai","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/S0140-6736(19)33174-5","article-title":"Emollients for Prevention of Atopic Dermatitis in Infancy","volume":"395","author":"Perrett","year":"2020","journal-title":"Lancet"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(19)32983-6","article-title":"Skin Emollient and Early Complementary Feeding to Prevent Infant Atopic Dermatitis (PreventADALL): A Factorial, Multicentre, Cluster-Randomised Trial","volume":"395","author":"Skjerven","year":"2020","journal-title":"Lancet"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/10\/1683\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:14:37Z","timestamp":1760138077000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/10\/1683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,19]]},"references-count":117,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["cells11101683"],"URL":"https:\/\/doi.org\/10.3390\/cells11101683","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,19]]}}}