{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:07:03Z","timestamp":1790478423825,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dermatopathology"],"abstract":"<jats:p>Whether the spongiotic reaction caused by the interaction of keratinocytes, T-lymphocytes, inflammatory dendritic epidermal cells (IDECs), and Langerhans cells (LCs) observed in atopic dermatitis (AD) represents a common feature of spongiosis in various skin diseases remains unclear. We analyzed the characteristics of spongiosis in AD compared with those in other eczematous dermatitis and inflammatory skin diseases by using immunohistochemical methods. Infiltration of IDECs (CD11c+ cells and\/or CD206+ cells) and T-lymphocytes, accompanied by degenerated keratinocytes and aggregated LCs (CD207+ cells), was frequently observed as a common feature of spongiosis in multiple conditions. However, IDECs expressing IgE were identified exclusively in IgE-mediated AD. Aggregation of IDECs was predominantly observed in the spongiosis of adaptive immune-mediated eczematous disorders, such as AD and allergic contact dermatitis. These IDEC aggregations constituted the major components of the epidermal dendritic cell clusters seen in AD and other eczematous or eczematoid dermatoses, and may serve as a useful distinguishing marker from Pautrier collections seen in cutaneous T-cell lymphoma. These findings suggest that IDECs, in cooperation with other immune cells, may play a pivotal role in spongiosis formation in AD and various skin diseases, although the underlying immunopathological mechanisms differ among these conditions.<\/jats:p>","DOI":"10.3390\/dermatopathology12030023","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T08:51:41Z","timestamp":1754038301000},"page":"23","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Immunohistopathological Analysis of Spongiosis Formation in Atopic Dermatitis Compared with Other Skin Diseases"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3774-2561","authenticated-orcid":false,"given":"Ryoji","family":"Tanei","sequence":"first","affiliation":[{"name":"Department of Dermatology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Itabashi, Tokyo 173-0015, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuko","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Geriatric Pathology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Itabashi, Tokyo 173-0015, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tanei, R., and Hasegawa, Y. (2022). Immunological Pathomechanisms of Spongiotic Dermatitis in Skin Lesions of Atopic Dermatitis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23126682"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Bieber, T., and Leung, D.Y.M. (2009). Role of T cells. Atopic Dermatitis, Informa Healthcare. [2nd ed.].","DOI":"10.1201\/9780367802875"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Clarke, L.E., Clarke, J.T., and Helm, K.F. (2014). Chapter 2: The Spongiotic and Psoriasiform Patterns. Color Atlas of Differential Diagnosis in Dermatopathology, Jaypee Brothers Medical Pub.. [1st ed.].","DOI":"10.5005\/jp\/books\/11980_2"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ad.2019.02.013","article-title":"Pigmented Purpuric Dermatosis: A Review of the Literature","volume":"111","author":"Biosca","year":"2020","journal-title":"Actas Dermosifiliogr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1111\/j.1365-2133.2009.09035.x","article-title":"Regulatory T cells in atopic dermatitis: Epidermal dendritic cell clusters may contribute to their local expansion","volume":"160","author":"Szegedi","year":"2009","journal-title":"Br. J. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1097\/00000372-199012000-00014","article-title":"A vase-like shape characterizes the epidermal-mononuclear cell collections seen in spongiotic dermatitis","volume":"12","author":"LeBoit","year":"1990","journal-title":"Am. J. Dermatopathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1034\/j.1600-0560.2002.290901.x","article-title":"Langerhans cell microgranulomas (pseudo-pautrier abscesses): Morphologic diversity, diagnostic implications and pathogenetic mechanisms","volume":"29","author":"Burkert","year":"2002","journal-title":"J. Cutan. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/cup.12595","article-title":"Spongiotic dermatitis with Langerhans cell microvesicles","volume":"43","author":"Howard","year":"2016","journal-title":"J. Cutan. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"747","DOI":"10.4103\/ijdvl.IJDVL_1100_19","article-title":"Pautrier\u2019s microabscess: An eponym by mistake","volume":"86","author":"Bhat","year":"2020","journal-title":"Indian J. Derm. Venereol. Leprol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"426","DOI":"10.3390\/dermatopathology8030045","article-title":"Immunohistopathological Analysis of Immunoglobulin E-Positive Epidermal Dendritic Cells with House Dust Mite Antigens in Naturally Occurring Skin Lesions of Adult and Elderly Patients with Atopic Dermatitis","volume":"8","author":"Tanei","year":"2021","journal-title":"Dermatopathology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"44","DOI":"10.2340\/00015555924447","article-title":"Diagnostic features of atopic dermatitis","volume":"92","author":"Hanifin","year":"1980","journal-title":"Acta Derm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1111\/j.1468-3083.2012.04612.x","article-title":"Abundant immunoglobulin E-positive cells in skin lesions support an allergic etiology of atopic dermatitis in the elderly","volume":"27","author":"Tanei","year":"2013","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_13","first-page":"134","article-title":"Double-positive immunoglobulin E+ and Dermatophagoides farinae antigen + dendritic cells are observed in skin lesions of older adults with atopic dermatitis: An immunohistological study","volume":"3","author":"Tanei","year":"2017","journal-title":"Dermatol. Clin. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ring, J., Przybilla, B., and Ruzicka, T. (2006). Inflammatory dendritic epidermal cells. Handbook of Atopic Eczema, Springer. [2nd ed.].","DOI":"10.1007\/3-540-29856-8"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1016\/j.jaci.2007.03.006","article-title":"Major differences in inflammatory dendritic cells and their products distinguish atopic dermatitis from psoriasis","volume":"119","author":"Lowes","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1067\/mai.2000.109825","article-title":"Down-regulation of IL-12 by topical corticosteroids in chronic atopic dermatitis","volume":"106","author":"Yawalkar","year":"2000","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0091-6749(96)70246-4","article-title":"In vivo expression of IL-12 and IL-13 in atopic dermatitis","volume":"98","author":"Hamid","year":"1996","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100021","DOI":"10.1016\/j.xjidi.2021.100021","article-title":"Cytokine RNA In Situ Hybridization Permits Individualized Molecular Phenotyping in Biopsies of Psoriasis and Atopic Dermatitis","volume":"1","author":"Wang","year":"2021","journal-title":"JID Innov."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.cyto.2015.05.019","article-title":"Mast Cell Production and Response to IL-4 and IL-13","volume":"75","author":"McLeod","year":"2015","journal-title":"Cytokine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1038\/ni.2992","article-title":"Perivascular leukocyte clusters are essential for efficient activation of effector T cells in the skin","volume":"15","author":"Natsuaki","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s00795-016-0137-4","article-title":"Inducible lymphoid clusters, iSALTs, in contact dermatitis: A new concept of acquired cutaneous immune responses","volume":"49","author":"Natsuaki","year":"2016","journal-title":"Med. Mol. Morphol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yamaguchi, H.L., Yamaguchi, Y., and Peeva, E. (2023). Role of Innate Immunity in Allergic Contact Dermatitis: An Update. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241612975"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wu, Z., Zheng, Y., Sheng, J., Han, Y., Yang, Y., Pan, H., and Yao, J. (2022). CD3+CD4-CD8- (Double-Negative) T Cells in Inflammation, Immune Disorders and Cancer. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.816005"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"212","DOI":"10.4049\/jimmunol.131.1.212","article-title":"Anti-Leu-3\/T4 antibodies react with cells of monocyte\/macrophage and Langerhans lineage","volume":"131","author":"Wood","year":"1983","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/hon.2850","article-title":"Cutaneous T-cell lymphomas\u2014An update 2021","volume":"39","author":"Kempf","year":"2021","journal-title":"Hematol. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/DAD.0000000000000842","article-title":"Histomorphology and Immunophenotype of Eczematous Skin Lesions Revisited\u2014Skin Biopsies Are Not Reliable in Differentiating Allergic Contact Dermatitis, Irritant Contact Dermatitis, and Atopic Dermatitis","volume":"40","author":"Frings","year":"2018","journal-title":"Am. J. Dermatopathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0167-5699(97)01046-3","article-title":"Fc\u03b5RI-expressing antigen-presenting cells: New players in atopic game","volume":"18","author":"Bieber","year":"1997","journal-title":"Immunol. Today"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.abd.2024.06.001","article-title":"Update on the pathogenesis of atopic dermatitis","volume":"99","author":"Criado","year":"2024","journal-title":"An. Bras. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s13555-025-01352-y","article-title":"Interleukin-4 and Atopic Dermatitis: Why Does it Matter? A Narrative Review","volume":"15","author":"Torres","year":"2025","journal-title":"Dermatol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1016\/j.jid.2023.03.1654","article-title":"Possible Involvement of Antigen-Presenting Cells Expressing the Macrophage Galactose-type C-type Lectin in Inflammatory Skin Diseases","volume":"143","author":"Murakami","year":"2023","journal-title":"J. Investig. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/nri723","article-title":"C-type lectin receptors on dendritic cells and Langerhans cells","volume":"2","author":"Carl","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s11882-023-01067-0","article-title":"C-Type Lectin Receptor Mediated Modulation of T2 Immune Responses to Allergens","volume":"23","author":"Angelina","year":"2023","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lee, W.-J., and Shim, W.-S. (2021). Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.772941"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1159\/000018220","article-title":"Nummular Eczema: An Addition of Senile Xerosis and Unique Cutaneous Reactivities to Environmental Aeroallergens","volume":"199","author":"Aoyama","year":"1999","journal-title":"Dermatology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S99","DOI":"10.1016\/S0091-6749(99)70051-5","article-title":"Pathogenesis of atopic dermatitis","volume":"104","author":"Leung","year":"1999","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.jaci.2004.02.005","article-title":"Fc epsilon RI engagement of Langerhans cell-like dendritic cells and inflammatory dendritic epidermal cell-like dendritic cells induces chemotactic signals and different T-cell phenotypes in vitro","volume":"113","author":"Novak","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.jaci.2005.10.040","article-title":"Absence of T-regulatory cell expression and unction in atopic dermatitis skin","volume":"117","author":"Verhagen","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1038\/jid.2008.394","article-title":"Increased hyaluronan production and decreased E-cadherin expression by cytokine-stimulated keratinocytes lead to spongiosis formation","volume":"129","author":"Ohtani","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.jaci.2014.03.009","article-title":"Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response","volume":"134","author":"Dhingra","year":"2014","journal-title":"J. Allergy Clin. Immunol."}],"container-title":["Dermatopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2296-3529\/12\/3\/23\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:20:43Z","timestamp":1760034043000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2296-3529\/12\/3\/23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,1]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["dermatopathology12030023"],"URL":"https:\/\/doi.org\/10.3390\/dermatopathology12030023","relation":{},"ISSN":["2296-3529"],"issn-type":[{"value":"2296-3529","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,1]]}}}