{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:00Z","timestamp":1787028480990,"version":"build-2736575974"},"reference-count":71,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T00:00:00Z","timestamp":1658880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Palmoplantar pustulosis (PPP) is a disease that causes recurrent blisters and aseptic pustules on the palms and soles. It has been suggested that both innate and acquired immunity are involved. In particular, based on the tonsils and basic experiments, it has been assumed that T and B cells are involved in its pathogenesis. In addition, the results of clinical trials have suggested that IL-23 is closely related to the pathogenesis. This review describes PPP and the genetic background, the factors involved in the onset and exacerbation of disease and its relation to the molecular mechanism. In addition, we describe the usefulness of biological therapy and its implications in relation to the importance in pathology, the pathogenesis of PPP, the importance of the role of the IL-23\u2013Th17 axis and IL-36 in PPP. Furthermore, we describe an animal experimental model of PPP, the efficacy and mechanism of action of guselkumab, an anti-IL-23 antibody, the latest research, and finally the possibility for it to be effective for other autoimmune diseases.<\/jats:p>","DOI":"10.3390\/ijms23158261","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T21:11:05Z","timestamp":1658956265000},"page":"8261","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Involvement of Molecular Mechanisms between T\/B Cells and IL-23: From Palmoplantar Pustulosis to Autoimmune Diseases"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6093-1881","authenticated-orcid":false,"given":"Takemichi","family":"Fukasawa","sequence":"first","affiliation":[{"name":"Department of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asako","family":"Yoshizaki-Ogawa","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Enomoto","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, The University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Miyagawa","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, The University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8194-9140","authenticated-orcid":false,"given":"Ayumi","family":"Yoshizaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/j.1346-8138.1993.tb01397.x","article-title":"Familial Cases of Psoriasis Vulgaris and Pustulosis Palmaris et Plantaris","volume":"20","author":"Matsuoka","year":"1993","journal-title":"J. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jdermsci.2018.01.012","article-title":"Autoinflammatory Keratinization Diseases: An Emerging Concept Encompassing Various Inflammatory Keratinization Disorders of the Skin","volume":"90","author":"Akiyama","year":"2018","journal-title":"J. Dermatol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/1346-8138.13551","article-title":"Mutation Analysis of IL36RN Gene in Japanese Patients with Palmoplantar Pustulosis","volume":"44","author":"Takahashi","year":"2017","journal-title":"J. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1111\/ced.13926","article-title":"A Novel CARD14 Variant, Homozygous c.526G>C (p.Asp176His), in an Adolescent Japanese Patient with Palmoplantar Pustulosis","volume":"44","author":"Tobita","year":"2019","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1038\/jid.2015.186","article-title":"Palmoplantar Pustular Psoriasis Is Associated with Missense Variants in CARD14, but Not with Loss-of-Function Mutations in IL36RN in European Patients","volume":"135","author":"Frambach","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.jaci.2018.06.038","article-title":"Clinical and Genetic Differences between Pustular Psoriasis Subtypes","volume":"143","author":"Twelves","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1111\/bjd.15867","article-title":"The Genetic Basis for Most Patients with Pustular Skin Disease Remains Elusive","volume":"178","author":"Oji","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.humimm.2011.03.009","article-title":"ATG16L1 Gene Polymorphisms Are Associated with Palmoplantar Pustulosis","volume":"72","author":"Douroudis","year":"2011","journal-title":"Hum. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"561","DOI":"10.2147\/CCID.S240607","article-title":"Diagnosis, Screening and Treatment of Patients with Palmoplantar Pustulosis (PPP): A Review of Current Practices and Recommendations","volume":"13","author":"Freitas","year":"2020","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s00403-015-1611-x","article-title":"Correlation of IL36RN Mutation with Different Clinical Features of Pustular Psoriasis in Chinese Patients","volume":"308","author":"Wang","year":"2016","journal-title":"Arch. Dermatol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1111\/j.1365-2133.2010.09819.x","article-title":"Novel Findings of Langerhans Cells and Interleukin-17 Expression in Relation to the Acrosyringium and Pustule in Palmoplantar Pustulosis","volume":"163","author":"Hagforsen","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1038\/jid.2010.87","article-title":"Acrosyringium Is the Main Site of the Vesicle\/Pustule Formation in Palmoplantar Pustulosis","volume":"130","author":"Murakami","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/ced.13689","article-title":"Interleukin (IL)-8 and IL-36\u03b3 but Not IL-36Ra Are Related to Acrosyringia in Pustule Formation Associated with Palmoplantar Pustulosis","volume":"44","author":"Xiaoling","year":"2019","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Murakami, M., Kaneko, T., Nakatsuji, T., Kameda, K., Okazaki, H., Dai, X., Hanakawa, Y., Tohyama, M., Ishida-Yamamoto, A., and Sayama, K. (2014). Vesicular LL-37 Contributes to Inflammation of the Lesional Skin of Palmoplantar Pustulosis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110677"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s40257-020-00503-5","article-title":"Palmoplantar Pustulosis: Recent Advances in Etiopathogenesis and Emerging Treatments","volume":"21","author":"Zozula","year":"2020","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1111\/1346-8138.15100","article-title":"Pathogenic Role of Palatine Tonsils in Palmoplantar Pustulosis: A Review","volume":"46","author":"Harabuchi","year":"2019","journal-title":"J. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.jaad.2005.07.024","article-title":"The Psoriasis Variant Palmoplantar Pustulosis Can Be Improved after Cessation of Smoking","volume":"54","author":"Gustafsson","year":"2006","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_18","first-page":"1375","article-title":"Analysis of 66 Cases of Pustulosis Palmaris et Plantaris Observed at Sapporo Medical University Hospital","volume":"122","author":"Kase","year":"2012","journal-title":"Jpn. J. Dermatol."},{"key":"ref_19","first-page":"1775","article-title":"A Statistical Analysis of 111 Cases of Pustulosis Palmaris et Plantaris during the Past 3 Years","volume":"125","author":"Fujishiro","year":"2015","journal-title":"Jpn. J. Dermatol."},{"key":"ref_20","first-page":"763","article-title":"Tonsillar Focal Infection-Present Clinical Situation and Prospects in the Future of Tonsillar Focal Infection","volume":"95","author":"Kataura","year":"2002","journal-title":"Pract. Otorhinolaryngol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1001\/archderm.1934.01460100066006","article-title":"Recalcitrant Pustular Eruptions Of The Palms And Soles","volume":"29","author":"Andrews","year":"1934","journal-title":"Arch. Derm. Syphilol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1111\/1346-8138.14348","article-title":"Treatment Outcome and Prognostic Factors of Tonsillectomy for Palmoplantar Pustulosis and Pustulotic Arthro-Osteitis: A Retrospective Subjective and Objective Quantitative Analysis of 138 Patients","volume":"45","author":"Takahara","year":"2018","journal-title":"J. Dermatol."},{"key":"ref_23","first-page":"821","article-title":"Efficacy of Treatment of Odontogenic Lesions in Palmoplantar Pustulosis","volume":"111","author":"Yamamoto","year":"2001","journal-title":"Jpn. J. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/1346-8138.13751","article-title":"Retrospective Analysis of the Clinical Response of Palmoplantar Pustulosis after Dental Infection Control and Dental Metal Removal","volume":"44","author":"Kouno","year":"2017","journal-title":"J. Dermatol."},{"key":"ref_25","first-page":"1539","article-title":"Treatment of Conditions That Are Difficult to Treat -Diagnosis and Treatment of Palmoplantar Pustulosis","volume":"60","author":"Kobayashi","year":"2018","journal-title":"Rinsho Derma"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e180","DOI":"10.1111\/jdv.15434","article-title":"Dental Metal Allergy Is Not the Main Cause of Palmoplantar Pustulosis","volume":"33","author":"Masui","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_27","first-page":"310","article-title":"Dental Focal Infection Associated with Skin Diseases. A Specific Reference to \u03b1-Hemolytic Cocci","volume":"43","author":"Iwai","year":"2001","journal-title":"J. Oral Biosci."},{"key":"ref_28","first-page":"143","article-title":"Focal Infection and Tonsillectomy","volume":"50","author":"Hayashi","year":"1996","journal-title":"Jpn. J. Clin. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jdermsci.2018.12.003","article-title":"Dysbiosis of Oral Microbiota in Palmoplantar Pustulosis Patients","volume":"93","author":"Kouno","year":"2019","journal-title":"J. Dermatol. Sci."},{"key":"ref_30","first-page":"1753","article-title":"Palmoplantar Pustulosis, Tonsillar Focal Infection","volume":"22","author":"Niizeki","year":"2006","journal-title":"JOHNS"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/imm.12891","article-title":"Autoimmunity and Autoimmune Co-Morbidities in Psoriasis","volume":"154","author":"Furue","year":"2018","journal-title":"Immunology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.anl.2008.11.009","article-title":"Pathogenic Role of Tonsillar Lymphocytes in Associated with HSP60\/65 in Pustulosis Palmaris et Plantaris","volume":"36","author":"Hayashi","year":"2009","journal-title":"Auris Nasus Larynx"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/j.1348-0421.2001.tb02651.x","article-title":"Engraftment of Tonsillar Mononuclear Cells in Human Skin\/SCID Mouse Chimera\u2014Validation of a Novel Xenogeneic Transplantation Model for Autoimmune Diseases","volume":"45","author":"Yamanaka","year":"2001","journal-title":"Microbiol. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1001\/jamadermatol.2017.5937","article-title":"Efficacy and Safety of Guselkumab, an Anti-Interleukin 23 Monoclonal Antibody, for Palmoplantar Pustulosis: A Randomized Clinical Trial","volume":"154","author":"Terui","year":"2018","journal-title":"JAMA Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1001\/jamadermatol.2019.1394","article-title":"Efficacy and Safety of Guselkumab in Japanese Patients With Palmoplantar Pustulosis: A Phase 3 Randomized Clinical Trial","volume":"155","author":"Terui","year":"2019","journal-title":"JAMA Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1111\/1346-8138.16132","article-title":"Sustained Efficacy and Safety of Guselkumab in Patients with Palmoplantar Pustulosis through 1.5 Years in a Randomized Phase 3 Study","volume":"48","author":"Okubo","year":"2021","journal-title":"J. Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1111\/jdv.16355","article-title":"Efficacy of Guselkumab in a Subpopulation with Pustulotic Arthro-Osteitis through Week 52: An Exploratory Analysis of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study in Japanese Patients with Palmoplantar Pustulosis","volume":"34","author":"Yamamoto","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1111\/1346-8138.13064","article-title":"Phase III Clinical Study of Maxacalcitol Ointment in Patients with Palmoplantar Pustulosis: A Randomized, Double-Blind, Placebo-Controlled Trial","volume":"43","author":"Umezawa","year":"2016","journal-title":"J. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3109\/09546634.2015.1052036","article-title":"Topical Combination Therapy with Vitamin D3 and Corticosteroid Ointment for Palmoplantar Pustulosis: A Prospective, Randomized, Left-Right Comparison Study","volume":"27","author":"Muro","year":"2016","journal-title":"J. Dermatol. Treat."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e198","DOI":"10.1111\/jdv.16909","article-title":"Short- and Long-Term Efficacy of Fumaric Acid Esters or Acitretin in Combination with a 12-Week Course of PUVA in the Treatment of Palmoplantar Pustulosis: Results from a Prospective Randomized Trial","volume":"35","author":"Aichelburg","year":"2021","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1007\/s10103-017-2280-0","article-title":"UVA1 vs. Narrowband UVB Phototherapy in the Treatment of Palmoplantar Pustulosis: A Pilot Randomized Controlled Study","volume":"32","author":"Su","year":"2017","journal-title":"Lasers Med. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/j.1365-2133.1991.tb04955.x","article-title":"A Double-Blind, Placebo-Controlled Trial of Topical PUVA in Persistent Palmoplantar Pustulosis","volume":"124","author":"Layton","year":"1991","journal-title":"Br. J. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e15079","DOI":"10.1111\/dth.15079","article-title":"A Randomized Prospective Study of Different Dose Regimens Using the 308-Nm Excimer Laser in the Treatment of Palmoplantar Pustulosis","volume":"34","author":"Peng","year":"2021","journal-title":"Dermatol. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e14650","DOI":"10.1111\/dth.14650","article-title":"Safety and Efficacy Profile of Oral Cyclosporine vs Oral Methotrexate vs Oral Acitretin in Palmoplantar Psoriasis: A Hospital Based Prospective Investigator Blind Randomized Controlled Comparative Study","volume":"34","author":"Shah","year":"2021","journal-title":"Dermatol. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e13486","DOI":"10.1111\/dth.13486","article-title":"Efficacy of Oral Methotrexate (MTX) Monotherapy vs Oral MTX plus Narrowband Ultraviolet Light B Phototherapy in Palmoplantar Psoriasis","volume":"33","author":"Ara","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1111\/bjd.14401","article-title":"Oral Alitretinoin Treatment in Patients with Palmoplantar Pustulosis Inadequately Responding to Standard Topical Treatment: A Randomized Phase II Study","volume":"174","author":"Reich","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1046\/j.1365-2133.1998.02555.x","article-title":"Double-Blind Placebo-Controlled Study of Long-Term Low-Dose Cyclosporin in the Treatment of Palmoplantar Pustulosis","volume":"139","author":"Erkko","year":"1998","journal-title":"Br. J. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1001\/archderm.1993.01680310043006","article-title":"Cyclosporine in the Treatment of Palmoplantar Pustulosis: A Randomized, Double-Blind, Placebo-Controlled Study","volume":"129","author":"Reitamo","year":"1993","journal-title":"Arch. Dermatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1159\/000249872","article-title":"A Randomized Trial of Etretinate (Tigason) in Palmoplantar Pustulosis","volume":"166","author":"Foged","year":"1983","journal-title":"Dermatologica"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1111\/jdv.17441","article-title":"A Multicentre Open-Label Study of Apremilast in Palmoplantar Pustulosis (APLANTUS)","volume":"35","author":"Kromer","year":"2021","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1111\/ijd.15382","article-title":"Immediate Response to Apremilast in Patients with Palmoplantar Pustulosis: A Retrospective Pilot Study","volume":"60","author":"Kato","year":"2021","journal-title":"Int. J. Dermatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s40257-021-00596-6","article-title":"Comparison of the Efficacy and Safety of Apremilast and Methotrexate in Patients with Palmoplantar Psoriasis: A Randomized Controlled Trial","volume":"22","author":"Kt","year":"2021","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1111\/j.1600-0625.2011.01325.x","article-title":"Patients with Palmoplantar Pustulosis Have Increased IL-17 and IL-22 Levels Both in the Lesion and Serum","volume":"20","author":"Murakami","year":"2011","journal-title":"Exp. Dermatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/bjd.20653","article-title":"Anakinra for Palmoplantar Pustulosis: Results from a Randomized, Double-Blind, Multicentre, Two-Staged, Adaptive Placebo-Controlled Trial (APRICOT)","volume":"186","author":"Cro","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/s13063-020-4103-z","article-title":"A Randomised Placebo Controlled Trial of Anakinra for Treating Pustular Psoriasis: Statistical Analysis Plan for Stage Two of the APRICOT Trial","volume":"21","author":"Cro","year":"2020","journal-title":"Trials"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s13555-021-00504-0","article-title":"Spesolimab, an Anti-Interleukin-36 Receptor Antibody, in Patients with Palmoplantar Pustulosis: Results of a Phase IIa, Multicenter, Double-Blind, Randomized, Placebo-Controlled Pilot Study","volume":"11","author":"Mrowietz","year":"2021","journal-title":"Dermatol. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1186\/s13063-018-2914-y","article-title":"Treatment of Pustular Psoriasis with Anakinra: A Statistical Analysis Plan for Stage 1 of an Adaptive Two-Staged Randomised Placebo-Controlled Trial","volume":"19","author":"Cro","year":"2018","journal-title":"Trials"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"McCluskey, D., Benzian-Olsson, N., Mahil, S.K., Hassi, N.K., Wohnhaas, C.T., Burden, A.D., Griffiths, C.E., Ingram, J.R., Levell, N.J., and Parslew, R. (2022). Single-Cell Analysis Implicates T H 17-to-T H 2 Cell Plasticity in the Pathogenesis of Palmoplantar Pustulosis. J. Allergy Clin. Immunol.","DOI":"10.1016\/j.jaci.2022.04.027"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1001\/jamadermatol.2020.3275","article-title":"Association of Clinical and Demographic Factors With the Severity of Palmoplantar Pustulosis","volume":"156","author":"Dand","year":"2020","journal-title":"JAMA Dermatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.jaci.2009.10.012","article-title":"Identification of a Novel Subset of Human Circulating Memory CD4+ T Cells That Produce Both IL-17A and IL-4","volume":"125","author":"Cosmi","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/j.jaci.2014.05.038","article-title":"Increased Frequency of Dual-Positive TH2\/TH17 Cells in Bronchoalveolar Lavage Fluid Characterizes a Population of Patients with Severe Asthma","volume":"134","author":"Irvin","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/nri.2017.50","article-title":"The Dichotomous Nature of T Helper 17 Cells","volume":"17","author":"Stockinger","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.coph.2014.06.004","article-title":"Th17 Plasticity: Pathophysiology and Treatment of Chronic Inflammatory Disorders","volume":"17","author":"Cosmi","year":"2014","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Xu, W., Li, R., and Sun, Y. (2019). Increased IFN-\u03b3-Producing Th17\/Th1 Cells and Their Association with Lung Function and Current Smoking Status in Patients with Chronic Obstructive Pulmonary Disease. BMC Pulm. Med., 19.","DOI":"10.1186\/s12890-019-0899-2"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e67209","DOI":"10.7554\/eLife.67209","article-title":"Single-Cell-Level Protein Analysis Revealing the Roles of Autoantigen-Reactive B Lymphocytes in Autoimmune Disease and the Murine Model","volume":"10","author":"Fukasawa","year":"2021","journal-title":"elife"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e489","DOI":"10.1016\/S2665-9913(21)00107-7","article-title":"Safety and Efficacy of Rituximab in Systemic Sclerosis (DESIRES): A Double-Blind, Investigator-Initiated, Randomised, Placebo-Controlled Trial","volume":"3","author":"Ebata","year":"2021","journal-title":"Lancet Rheumatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"7200","DOI":"10.1039\/C9AN01702J","article-title":"Cytokine Analysis on a Countable Number of Molecules from Living Single Cells on Nanofluidic Devices","volume":"144","author":"Nakao","year":"2019","journal-title":"Analyst"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1002\/art.40164","article-title":"Contribution of Soluble Forms of Programmed Death 1 and Programmed Death Ligand 2 to Disease Severity and Progression in Systemic Sclerosis","volume":"69","author":"Fukasawa","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"16010","DOI":"10.1038\/s41598-019-52435-8","article-title":"Prevention of Calpain-Dependent Degradation of STK38 by MEKK2-Mediated Phosphorylation","volume":"9","author":"Enomoto","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1080\/02656736.2021.2024281","article-title":"Decrease in MAP3Ks Expression Enhances the Cell Death Caused by Hyperthermia","volume":"39","author":"Enomoto","year":"2022","journal-title":"Int. J. Hyperth."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5947","DOI":"10.1038\/s41467-021-26099-w","article-title":"Interleukin-31 Promotes Fibrosis and T Helper 2 Polarization in Systemic Sclerosis","volume":"12","author":"Kuzumi","year":"2021","journal-title":"Nat. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8261\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:57:09Z","timestamp":1760140629000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8261"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,27]]},"references-count":71,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23158261"],"URL":"https:\/\/doi.org\/10.3390\/ijms23158261","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,27]]}}}