{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:16:28Z","timestamp":1778220988793,"version":"3.51.4"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"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":"\n Background<\/jats:title>\n Acquired idiopathic generalized anhidrosis (AIGA) is a rare disorder characterized by generalized loss of sweating without identifiable causes. Because few biomarkers reflect its underlying mechanisms, diagnosis at the initial visit is often difficult. Although steroid pulse therapy is widely used, approximately half of patients respond insufficiently. We therefore aimed to elucidate the immune mechanisms underlying AIGA and identify potential biomarkers for diagnosis and treatment response.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Fourteen patients with AIGA affecting more than 25% of body surface area were enrolled after exclusion of secondary causes of anhidrosis. Serum levels of 40 cytokines and chemokines were quantified using a multiplex assay and correlated with clinical parameters. Skin biopsy specimens were analyzed by histology and immunohistochemistry to characterize inflammatory cell infiltration and identify cellular sources of selected mediators.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Inflammatory cell infiltration was consistently observed around sweat ducts, predominantly composed of CD4\n +<\/jats:sup>\n T cells. Serum profiling revealed significant elevations of CCL22 and IFN-\u03b3 in AIGA compared with healthy controls, with a strong positive correlation between them. Consistently, the downstream chemokine CXCL10 was also increased. Double immunostaining identified CD68\n +<\/jats:sup>\n macrophages as the main source of CCL22 in periductal regions. Serum Macrophage migration inhibitory factor (MIF) levels were significantly higher in steroid-resistant cases, whereas MIF expression within sweat ducts was markedly reduced, suggesting disruption of local immune privilege.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n These findings suggest that AIGA involves a macrophage\u2013CCL22\u2013Th1\u2013IFN-\u03b3 inflammatory axis associated with collapse of sweat duct immune privilege. Serum MIF may serve as a potential biomarker for predicting steroid responsiveness.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1831853","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:54:58Z","timestamp":1778219698000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CCL22-producing macrophages are associated with Th1-related sweat duct inflammation in acquired idiopathic generalized anhidrosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Shingo","family":"Takei","sequence":"first","affiliation":[{"name":"Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences","place":["Niigata, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryota","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences","place":["Niigata, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manon","family":"Okamura","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences","place":["Niigata, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuya","family":"Katsumi","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences","place":["Niigata, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toru","family":"Kawai","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences","place":["Niigata, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riichiro","family":"Abe","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences","place":["Niigata, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1111\/1346-8138.13649","article-title":"Revised guideline for the diagnosis and treatment of acquired idiopathic generalized anhidrosis in Japan","volume":"44","author":"Munetsugu","year":"2017","journal-title":"J Dermatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.13390","article-title":"Serum carcinoembryonic antigen (CEA) as a clinical marker in acquired idiopathic generalized anhidrosis: a close correlation between serum CEA level and disease activity","volume":"30","author":"Honma","year":"2016","journal-title":"J Eur Acad Dermatol Venereol JEADV"},{"key":"B3","doi-asserted-by":"crossref","unstructured":"Steroid treatment can improve the impaired quality of life of patients with acquired idiopathic generalized anhidrosis\n \n \n \n Fukunaga\n A\n \n \n Hatakeyama\n M\n \n \n Tsujimoto\n M\n \n \n Oda\n Y\n \n \n Washio\n K\n \n \n Nishigori\n C\n \n \n Br J Dermatol\n 172\n 2015","DOI":"10.1111\/bjd.13285"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.15666","article-title":"Prognosis after steroid pulse therapy and seasonal effect in acquired idiopathic generalized anhidrosis","volume":"48","author":"Iida","year":"2021","journal-title":"J Dermatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.19284","article-title":"Type 1 interferon signature and cytotoxic T lymphocyte activation targeted against sweat ducts in inflammatory acquired idiopathic generalized anhidrosis","volume":"37","author":"Sano","year":"2023","journal-title":"J Eur Acad Dermatol Venereol JEADV"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5701183","article-title":"Maintenance of hair follicle immune privilege is linked to prevention of NK 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Ther"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2020.10.015","article-title":"Digital immunohistological dissection of immune privilege collapse in syringotropic autoimmune diseases: implication for the pathogenesis","volume":"101","author":"Shimoda-Komatsu","year":"2021","journal-title":"J Dermatol Sci"},{"key":"B11","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jdermsci.2022.10.001","article-title":"Clinicopathological digital image analyses before and after thermal stimulation subdivide acquired idiopathic generalized anhidrosis into inflammatory and non-inflammatory type","volume":"108","author":"Shimoda-Komatsu","year":"2022","journal-title":"J Dermatol Sci"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/s1074-7613(02)00331-x","article-title":"Further checkpoints in Th1 development","volume":"16","author":"Robinson","year":"2002","journal-title":"Immunity"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.6.4149","article-title":"CCR4 participation in Th type 1 (Mycobacterial) and Th type 2 (Schistosomal) anamnestic pulmonary granulomatous responses","volume":"177","author":"Freeman","year":"2006","journal-title":"J Immunol Baltim Md 1950"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02594","article-title":"CCL22-producing resident macrophages enhance T cell response in Sj\u00f6gren\u2019s syndrome","volume":"9","author":"Ushio","year":"2018","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1831853\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:55:03Z","timestamp":1778219703000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1831853\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":14,"alternative-id":["10.3389\/fimmu.2026.1831853"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1831853","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]},"article-number":"1831853"}}