{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:51:01Z","timestamp":1790009461061,"version":"4.0.1"},"reference-count":27,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T00:00:00Z","timestamp":1722556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"LEO Pharma, the DFG Research Unit PruSearch FOR 2690","award":["AG 271\/1-2"],"award-info":[{"award-number":["AG 271\/1-2"]}]},{"name":"LEO Pharma, the DFG Research Unit PruSearch FOR 2690","award":["STA 1159\/4-2"],"award-info":[{"award-number":["STA 1159\/4-2"]}]},{"name":"LEO Pharma, the DFG Research Unit PruSearch FOR 2690","award":["STA 1159\/6-2"],"award-info":[{"award-number":["STA 1159\/6-2"]}]},{"name":"LEO Pharma, the DFG Research Unit PruSearch FOR 2690","award":["STA 1159\/7-1"],"award-info":[{"award-number":["STA 1159\/7-1"]}]},{"name":"DFG Research Unit SOMACROSS FOR5211","award":["AG 271\/1-2"],"award-info":[{"award-number":["AG 271\/1-2"]}]},{"name":"DFG Research Unit SOMACROSS FOR5211","award":["STA 1159\/4-2"],"award-info":[{"award-number":["STA 1159\/4-2"]}]},{"name":"DFG Research Unit SOMACROSS FOR5211","award":["STA 1159\/6-2"],"award-info":[{"award-number":["STA 1159\/6-2"]}]},{"name":"DFG Research Unit SOMACROSS FOR5211","award":["STA 1159\/7-1"],"award-info":[{"award-number":["STA 1159\/7-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The clinical manifestations of atopic dermatitis (AD) and chronic nodular prurigo (CNPG) include pruritus and eczema\/lesions, posing significant challenges for patients. Th2 cells and ILC2, marked by cytokine production\u2014particularly IL-4\/13\u2014are crucial therapeutic targets. Despite displaying a dose-dependent lack of pruritus induction post-injection, IL-13 acts through the IL-13R\u03b11 and IL-13R\u03b12 receptor system. Our study focused on investigating ex vivo skin biopsies in AD (n = 17), CNPG (n = 14) and healthy controls (HC; n = 10), examining the gene expression landscape of interleukins linked with pruritus (IL-13, IL-4, IL-31) and their corresponding receptors. Compared to HC, results revealed a significant upregulation of IL-4, IL-13, and IL-13RA1 in AD, whereas CNPG did not show increased IL13 expression. Notably, the decoy receptor IL-13RA2 displayed intriguing patterns, with AD showing a marked increase compared to both HC and CNPG. Positive correlations between receptor expression and itch intensity and hyperkinesis sensation underscore clinical relevance, potentially serving as biomarkers. The findings suggest a pivotal role of IL-4 and IL-13, along with IL-13RA1, in pruritus pathogenesis in both entities, while IL-13 upregulation in AD is countered by IL-13RA2. The comparable expression of IL-13RA2 to HC in CNPG suggests the absence of this regulatory mechanism, potentially worsening the disease and leading to prolonged scratching behavior. These insights illuminate the intricate interplay of interleukins and receptors in different pruritus phenotypes, laying the groundwork for understanding underlying mechanisms and offering avenues for therapeutic intervention.<\/jats:p>","DOI":"10.3390\/ijms25158445","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T13:14:42Z","timestamp":1722604482000},"page":"8445","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Interleukin Profiling in Atopic Dermatitis and Chronic Nodular Prurigo"],"prefix":"10.3390","volume":"25","author":[{"given":"Henning","family":"Wiegmann","sequence":"first","affiliation":[{"name":"Section Pruritus Medicine and Center for Chronic Pruritus, Department of Dermatology, University of Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Renkhold","sequence":"additional","affiliation":[{"name":"Section Pruritus Medicine and Center for Chronic Pruritus, Department of Dermatology, University of Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Zeidler","sequence":"additional","affiliation":[{"name":"Section Pruritus Medicine and Center for Chronic Pruritus, Department of Dermatology, University of Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Agelopoulos","sequence":"additional","affiliation":[{"name":"Section Pruritus Medicine and Center for Chronic Pruritus, Department of Dermatology, University of Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3612-7786","authenticated-orcid":false,"given":"Sonja","family":"St\u00e4nder","sequence":"additional","affiliation":[{"name":"Section Pruritus Medicine and Center for Chronic Pruritus, Department of Dermatology, University of Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20406223221112561","DOI":"10.1177\/20406223221112561","article-title":"Increased IL-31 expression in serum and tissue protein in prurigo nodularis","volume":"13","author":"Chaowattanapanit","year":"2022","journal-title":"Ther. Adv. Chronic Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/j.jaci.2021.10.004","article-title":"Transcriptomic characterization of prurigo nodularis and the therapeutic response to nemolizumab","volume":"149","author":"Tsoi","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Klonowska, J., Gle\u0144, J., Roman Nowicki Nowicki, R., and Trzeciak, M. (2018). New Cytokines in the Pathogenesis of Atopic Dermatitis\u2014New Therapeutic Targets. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19103086"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Garcovich, S., Maurelli, M., Gisondi, P., Peris, K., Yosipovitch, G., and Girolomoni, G. (2021). Pruritus as a distinctive feature of type 2 inflammation. Vaccines, 9.","DOI":"10.3390\/vaccines9030303"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Meng, J., Li, Y., Fischer, M.J.M., Steinhoff, M., Chen, W., and Wang, J. (2021). Th2 modulation of transient receptor potential channels: An unmet therapeutic intervention for atopic dermatitis. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.696784"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1080\/1744666X.2021.1940962","article-title":"The IL-4, IL-13 and IL-31 pathways in atopic dermatitis","volume":"17","author":"Dubin","year":"2021","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S1074-7613(02)00332-1","article-title":"IL-4 induces characteristic Th2 responses even in the combined absence of IL-5, IL-9, and IL-13","volume":"17","author":"Fallon","year":"2002","journal-title":"Immunity"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"110","DOI":"10.4172\/2155-9899.1000110","article-title":"Th2 Cytokines and Atopic Dermatitis","volume":"2","author":"Brandt","year":"2011","journal-title":"J. Clin. Cell. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1056\/NEJMoa1610020","article-title":"Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis","volume":"375","author":"Simpson","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ulzii, D., Kido-Nakahara, M., Nakahara, T., Tsuji, G., Furue, K., Hashimoto-Hachiya, A., and Furue, M. (2019). Scratching Counteracts IL-13 Signaling by Upregulating the Decoy Receptor IL-13R\u03b12 in Keratinocytes. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133324"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1111\/all.13814","article-title":"Periostin: An emerging biomarker for allergic diseases","volume":"74","author":"Izuhara","year":"2019","journal-title":"Allergy"},{"key":"ref_12","first-page":"62","article-title":"The impact of mast cells in neuroimmunology and cancer","volume":"12","author":"Pandolfi","year":"2023","journal-title":"Eur. J. Neurodegener. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e2250359","DOI":"10.1002\/eji.202250359","article-title":"Mast cells in type 2 skin inflammation: Maintenance and function","volume":"53","author":"Keith","year":"2023","journal-title":"Eur. J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.jid.2019.05.029","article-title":"Peripheral Sensitization and Loss of Descending Inhibition Is a Hallmark of Chronic Pruritus","volume":"140","author":"Pereira","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jid.2022.08.042","article-title":"Transcriptomic, Epigenomic, and Neuroanatomic Signatures Differ in Chronic Prurigo, Atopic Dermatitis, and Brachioradial Pruritus","volume":"143","author":"Agelopoulos","year":"2023","journal-title":"J. Investig. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1111\/exd.14034","article-title":"Interleukin-4 and interleukin-13 evoke scratching behaviour in mice","volume":"28","author":"Campion","year":"2019","journal-title":"Exp. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Leyva-Castillo, J.M., Das, M., Strakosha, M., McGurk, A., Artru, E., Kam, C., Alasharee, M., Wesemann, D.R., Tomura, M., and Karasuyama, H. (2024). IL-4 acts on skin derived dendritic cells to promote the Th2 response to cutaneous sensitization and the development of allergic skin inflammation. J. Allergy Clin. Immunol., in press.","DOI":"10.1016\/j.jaci.2024.06.021"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.alit.2020.01.005","article-title":"Implications of IL-13R\u03b12 in atopic skin inflammation","volume":"69","author":"Furue","year":"2020","journal-title":"Allergol. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.bbi.2021.08.211","article-title":"Innate immune regulates cutaneous sensory IL-13 receptor alpha 2 to promote atopic dermatitis","volume":"98","author":"Xiao","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Umehara, Y., Kiatsurayanon, C., Trujillo-Paez, J.V., Chieosilapatham, P., Peng, G., Yue, H., Nguyen, H.L.T., Song, P., Okumura, K., and Ogawa, H. (2021). Intractable Itch in Atopic Dermatitis: Causes and Treatments. Biomedicines, 9.","DOI":"10.3390\/biomedicines9030229"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1097\/j.pain.0000000000001220","article-title":"Alloknesis and hyperknesis-mechanisms, assessment methodology, and clinical implications of itch sensitization","volume":"159","author":"Andersen","year":"2018","journal-title":"Pain"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/jdv.15973","article-title":"Neuroimmune interactions in chronic itch of atopic dermatitis","volume":"34","author":"Yosipovitch","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.molmed.2022.03.005","article-title":"Cutaneous neuroimmune crosstalk in pruritus","volume":"28","author":"Agelopoulos","year":"2022","journal-title":"Trends Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.36849\/JDD.7249","article-title":"Unexpected Clinical Lessons Learned From IL-4 and IL-13 Blockade","volume":"22","author":"Bury","year":"2023","journal-title":"J. Drugs Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Mack, M.R., Miron, Y., Chen, F., Miller, P.E., Zhang, A., Korotzer, A., Richman, D., and Bryce, P.J. (2023). Type 2 cytokines sensitize human sensory neurons to itch-associated stimuli. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1258823"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1093\/bjd\/ljae052","article-title":"Prurigo nodularis: New insights into pathogenesis and novel therapeutics","volume":"190","author":"Liao","year":"2024","journal-title":"Br. J. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v036.i11","article-title":"Feature Selection with the Boruta Package","volume":"36","author":"Kursa","year":"2010","journal-title":"J. Stat. Softw."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8445\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:28:47Z","timestamp":1760110127000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8445"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,2]]},"references-count":27,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25158445"],"URL":"https:\/\/doi.org\/10.3390\/ijms25158445","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,2]]}}}