{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T07:01:35Z","timestamp":1780038095642,"version":"3.53.1"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background and objective<\/jats:title>\n                    <jats:p>Atopic dermatitis (AD) is a chronic immune-mediated inflammatory skin disease characterized by persistent pruritus and eczematous lesions. Its core pathophysiology involves Th2-skewed immune responses and epidermal barrier dysfunction. Plasmacytoid dendritic cells (pDCs), known for their potent production of type I interferons, have demonstrated immunomodulatory roles in various diseases, including allergic asthma. However, their specific function and underlying mechanisms in AD remain poorly defined. This study aims to investigate the role of pDCs in AD and elucidate their molecular regulatory pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We employed an integrative approach combining transcriptomic analysis, flow cytometry, an MC903-induced murine model of AD,\n                      <jats:italic>in vivo<\/jats:italic>\n                      expansion of pDCs using FLT3L, targeted depletion of pDCs with the 120G8 antibody, and IFNAR1-deficient mice. These complementary strategies were used to systematically evaluate the distribution, activation status, and immunological function of pDCs in AD, as well as the mechanisms involved.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>pDCs were significantly elevated in the peripheral blood of AD patients and were associated with increased expression of Th2 cytokines. In the MC903-induced murine model, pDCs showed dynamic accumulation in skin lesions and draining lymph nodes. Expansion of pDCs by FLT3L markedly alleviated AD-like skin inflammation, suppressed Th2 cytokines (IL-4, IL-13) and IgE production, and enhanced the expression of epidermal barrier proteins. In contrast, depletion of pDCs by 120G8 exacerbated the inflammatory phenotype. Importantly, the anti-inflammatory effects of pDCs were abolished in IFNAR1-deficient mice, indicating that pDCs exert their immunosuppressive function in AD primarily through the IFN-\u03b1\/IFNAR signaling axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study is the first to systematically demonstrate the immunosuppressive role of pDCs in AD. We show that pDCs negatively regulate Th2 inflammation and maintain barrier integrity via the IFN-\u03b1\/IFNAR1 pathway. These findings provide a theoretical and experimental foundation for targeting pDCs and their downstream signaling as a novel therapeutic strategy in AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1762173","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:02:52Z","timestamp":1780034572000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasmacytoid dendritic cells alleviate atopic dermatitis by suppressing Th2 inflammation via the IFN-\u03b1\/IFNAR1 pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Jun-rong","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Dermatology, Hubei Provincial Hospital of Traditional Chinese Medicine (Affiliated Hospital of Hubei University of Chinese Medicine, Hubei Provincial Academy of Traditional Chinese Medicine)","place":["Wuhan, China"]},{"name":"Department of Dermatology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-hua","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang-shang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)31286-1","article-title":"Atopic dermatitis","volume":"396","author":"Langan","year":"2020","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.jid.2016.07.012","article-title":"The burden of atopic dermatitis: Summary of a report for the National Eczema Association","volume":"137","author":"Drucker","year":"2017","journal-title":"J Invest Dermatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22084130","article-title":"Molecular mechanisms of atopic dermatitis pathogenesis","volume":"22","author":"Sroka-Tomaszewska","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/srep29751","article-title":"Prevalence of atopic dermatitis in Chinese children aged 1-7\u2009ys","volume":"6","author":"Guo","year":"2016","journal-title":"Sci Rep"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.08.001","article-title":"Distinct behavior of human Langerhans cells and inflammatory dendritic epidermal cells at tight junctions in patients with atopic dermatitis","volume":"134","author":"Yoshida","year":"2014","journal-title":"J Allergy Clin Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.10.015","article-title":"Upregulation of type 1 conventional dendritic cells implicates antigen cross-presentation in multisystem inflammatory syndrome","volume":"149","author":"Huang","year":"2022","journal-title":"J Allergy Clin Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-031210-101345","article-title":"Plasmacytoid dendritic cells: Recent progress and open questions","volume":"29","author":"Reizis","year":"2011","journal-title":"Annu Rev Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12315","article-title":"Plasmacytoid dendritic cells suppress Th2 responses induced by epicutaneous sensitization","volume":"98","author":"Lin","year":"2020","journal-title":"Immunol Cell Biol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.02.011","article-title":"Plasmacytoid dendritic cells: Welcome back to the DC fold","volume":"55","author":"Reynolds","year":"2022","journal-title":"Immunity"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101102","article-title":"Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons","volume":"207","author":"Gregorio","year":"2010","journal-title":"J Exp Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2025.01.047","article-title":"Plasmacytoid dendritic cells alleviate allergic asthma via airway epithelial cell-dependent thymosin \u03b24 expression","volume":"156","author":"Li","year":"2025","journal-title":"J Allergy Clin Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1554492","article-title":"Sequential activation of conventional and plasmacytoid dendritic cells in autoimmune pancreatitis and systemic lupus erythematosus: Similarities and dissimilarities","volume":"16","author":"Hara","year":"2025","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2019.07.009","article-title":"Plasmacytoid dendritic cells as a possible key player to initiate alopecia areata in the C3H\/HeJ mouse","volume":"69","author":"Ito","year":"2020","journal-title":"Allergol Int"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nri3865","article-title":"The multifaceted biology of plasmacytoid dendritic cells","volume":"15","author":"Swiecki","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1186\/s13059-017-1349-1","article-title":"xCell: Digitally portraying the tissue cellular heterogeneity landscape","volume":"18","author":"Dvir Aran","year":"2017","journal-title":"Genome Biol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1016\/j.immuni.2023.03.002","article-title":"Maternal diet modulates the infant microbiome and intestinal Flt3L necessary for dendritic cell development and immunity to respiratory infection","volume":"56","author":"Sikder","year":"2023","journal-title":"Immunity"},{"key":"B17","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1186\/s13075-018-1702-0","article-title":"Cytokine production by activated plasmacytoid dendritic cells and natural killer cells is suppressed by an IRAK4 inhibitor","volume":"20","author":"Hjorton","year":"2018","journal-title":"Arthritis Res Ther"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-090122-041105","article-title":"Ontogeny and function of plasmacytoid dendritic cells","volume":"42","author":"Adams","year":"2024","journal-title":"Annu Rev Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.add4132","article-title":"pDC-like cells are pre-DC2 and require KLF4 to control homeostatic CD4 T cells","volume":"8","author":"Rodrigues","year":"2023","journal-title":"Sci Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1762173\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:02:53Z","timestamp":1780034573000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1762173\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":19,"alternative-id":["10.3389\/fimmu.2026.1762173"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1762173","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"article-number":"1762173"}}