{"doi":"10.1111/imm.12446","title":"Progranulin is preferentially expressed in patients with psoriasis vulgaris and protects mice from psoriasis‐like skin inflammation","abstract":"<jats:title>Summary</jats:title><jats:p>Progranulin (<jats:styled-content style=\"fixed-case\">PGRN</jats:styled-content>) is a multi‐functional protein known to be involved in inflammation. Recent studies have found that <jats:styled-content style=\"fixed-case\">PGRN</jats:styled-content> has dual roles in inflammation and exerts anti‐inflammatory and pro‐inflammatory function in different diseases. However, the role of <jats:styled-content style=\"fixed-case\">PGRN</jats:styled-content> in psoriasis has not been fully elucidated. Here, we detected preferential expression of <jats:styled-content style=\"fixed-case\">PGRN</jats:styled-content> in human psoriatic lesions and serum. Moreover, serum <jats:styled-content style=\"fixed-case\">PGRN</jats:styled-content>/tumour necrosis factor‐<jats:italic>α</jats:italic> ratio was negatively correlated with disease severity. To investigate the role of <jats:styled-content style=\"fixed-case\">PGRN</jats:styled-content> in the pathogenesis of psoriasis, we used wild‐type (<jats:styled-content style=\"fixed-case\">WT</jats:styled-content>) and <jats:styled-content style=\"fixed-case\">PGRN</jats:styled-content><jats:sup>−/−</jats:sup> mice in a model of 12‐<jats:italic>O</jats:italic>‐tetradecanoylphorbol 13‐acetate (<jats:styled-content style=\"fixed-case\">TPA</jats:styled-content>) ‐induced psoriasis‐like inflammation. We demonstrated that <jats:styled-content style=\"fixed-case\">PGRN</jats:styled-content> expression was dramatically enhanced in the psoriasis‐like lesions of <jats:styled-content style=\"fixed-case\">TPA</jats:styled-content>‐treated <jats:styled-content style=\"fixed-case\">WT</jats:styled-content> mice, in accordance with human psoriatic lesions. Surprisingly, <jats:styled-content style=\"fixed-case\">PGRN</jats:styled-content><jats:sup>−/−</jats:sup> mice were more sensitive to the development of <jats:styled-content style=\"fixed-case\">TPA</jats:styled-content>‐induced psoriasis‐like inflammation. The mechanism underlying this increased sensitivity of <jats:styled-content style=\"fixed-case\">PGRN</jats:styled-content><jats:sup>−/−</jats:sup> mice to <jats:styled-content style=\"fixed-case\">TPA</jats:styled-content>‐induced psoriasis‐like inflammation was impaired differentiation of regulatory T cells in lymph nodes and decreased recruitment of these cells in the affected skin, which results in more severe inflammation. Hence, in <jats:styled-content style=\"fixed-case\">WT</jats:styled-content> mice, <jats:styled-content style=\"fixed-case\">PGRN</jats:styled-content> promotes differentiation and recruitment of regulatory T cells at the site of inflammation, which protects the skin from an exaggerated psoriasis‐like inflammatory response.</jats:p>","journal":"Immunology","year":2015,"id":604039,"datarank":0.62147020895873,"base_score":4.143134726391533,"endowment":4.143134726391533,"self_citation_contribution":0.62147020895873,"citation_network_contribution":0.0,"self_endowment_contribution":0.62147020895873,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":62,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1549690,"name":"Aijun Chen","orcid":null,"position":1,"is_corresponding":false},{"id":738695,"name":"Xuemei Zhang","orcid":"0000-0003-0705-4231","position":2,"is_corresponding":false},{"id":1549694,"name":"Zhixin Song","orcid":null,"position":3,"is_corresponding":false},{"id":381102,"name":"Hongmei Xu","orcid":"0000-0002-8650-8694","position":4,"is_corresponding":false},{"id":1549695,"name":"Ju Cao","orcid":null,"position":5,"is_corresponding":false},{"id":1549696,"name":"Yibing Yin","orcid":null,"position":6,"is_corresponding":false},{"id":653154,"name":"Kun Huang","orcid":"0000-0002-2021-9910","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Progranulin is preferentially expressed in patients with psoriasis vulgaris and protects mice from psoriasis‐like skin inflammation","abstract":"Progranulin (PGRN) is a multi-functional protein known to be involved in inflammation. Recent studies have found that PGRN has dual roles in inflammation and exerts anti-inflammatory and pro-inflammatory function in different diseases. However, the role of PGRN in psoriasis has not been fully elucidated. Here, we detected preferential expression of PGRN in human psoriatic lesions and serum. Moreover, serum PGRN/tumour necrosis factor-α ratio was negatively correlated with disease severity. To investigate the role of PGRN in the pathogenesis of psoriasis, we used wild-type (WT) and PGRN(-/-) mice in a model of 12-O-tetradecanoylphorbol 13-acetate (TPA) -induced psoriasis-like inflammation. We demonstrated that PGRN expression was dramatically enhanced in the psoriasis-like lesions of TPA-treated WT mice, in accordance with human psoriatic lesions. Surprisingly, PGRN(-/-) mice were more sensitive to the development of TPA-induced psoriasis-like inflammation. The mechanism underlying this increased sensitivity of PGRN(-/-) mice to TPA-induced psoriasis-like inflammation was impaired differentiation of regulatory T cells in lymph nodes and decreased recruitment of these cells in the affected skin, which results in more severe inflammation. Hence, in WT mice, PGRN promotes differentiation and recruitment of regulatory T cells at the site of inflammation, which protects the skin from an exaggerated psoriasis-like inflammatory response.","is_dataset_classified":null,"base_score":4.143134726391533,"endowment":4.143134726391533,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25626394","pmcid":null,"openalex_id":"https://openalex.org/W2040712189","authors":[],"funders":[{"funder_name":"National Natural Science Foundation grants of China","grant_id":"81402606","title":null}],"total_grants":1,"fwci":1.5162,"citation_percentile":0.81774547,"influential_citations":0,"citation_trend":[{"year":2015,"count":2},{"year":2016,"count":4},{"year":2017,"count":1},{"year":2018,"count":5},{"year":2019,"count":13},{"year":2020,"count":7},{"year":2021,"count":6},{"year":2022,"count":6},{"year":2023,"count":2},{"year":2024,"count":13},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/imm.12446","host_type":"journal"},{"url":"https://doi.org/10.1111/imm.12446","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25626394","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4427392","host_type":"repository"}],"fields_of_study":["Psoriasis: Treatment and Pathogenesis","Amyotrophic Lateral Sclerosis Research","Neuroinflammation and Neurodegeneration Mechanisms"],"mesh_terms":["Progranulins","Granulins","Adult","Animals","Carcinogens","Cell Differentiation","Disease Models, Animal","Female","Gene Expression Regulation","Humans","Inflammation","Male","Middle Aged","Psoriasis","Skin","Tetradecanoylphorbol Acetate","Mice, Knockout","Intercellular Signaling Peptides and Proteins","T-Lymphocytes, Regulatory","Mice"],"keywords":["Psoriasis","Inflammation","Tumor necrosis factor alpha","Pathogenesis","Immunology","Medicine","Interleukin 23","Interleukin 17","Regulatory T cells","Progranulin"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T23:15:44.905871Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}