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Traditional treatments, such as immunosuppressive drugs, only provide symptomatic relief and often cause significant side effects. Cold atmospheric plasma (CAP), a form of nonthermal plasma, has emerged as a potential therapeutic tool, offering antimicrobial, anti\u2010inflammatory, and immune\u2010modulatory effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This review aims to explore the mechanisms of CAP, its application in autoimmune diseases, and its potential to improve existing treatments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The review synthesizes recent studies investigating the biological effects of CAP, particularly its interaction with immune cells. Key mechanisms discussed include the generation of reactive oxygen and nitrogen species (ROS\/RNS), which modulate immune responses, promote wound healing, and target pathogenic cells. The therapeutic potential of CAP in treating autoimmune diseases, such as RA, atopic dermatitis, allergic contact dermatitis, psoriasis, and vitiligo is examined through current research findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Studies have demonstrated that CAP can modulate fibroblast\u2010like synoviocytes in RA, reducing their viability and inducing apoptosis. In skin diseases like atopic dermatitis, CAP has been shown to alleviate symptoms and reduce microbial load by altering the skin microbiome. In psoriasis, CAP suppresses Th17 cell differentiation and reduces keratinocyte hyperproliferation. Additionally, CAP enhances wound healing by promoting macrophage M2 polarization and collagen remodeling. Despite promising results, concerns remain about the long\u2010term safety of CAP, particularly regarding the accumulation of ROS\/RNS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CAP offers a novel approach for treating autoimmune diseases by modulating immune responses, enhancing drug efficacy, and promoting tissue repair. Its ability to selectively target pathogenic cells and its antimicrobial properties make it a promising therapeutic tool in autoimmune diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.70245","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T10:52:09Z","timestamp":1755082329000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cold Atmospheric Plasma in the Treatment of Autoimmune Diseases: Mechanisms, Applications, and Prospects"],"prefix":"10.1002","volume":"13","author":[{"given":"Zhenyu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minglong","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0828-1583","authenticated-orcid":false,"given":"Zhu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3897"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","unstructured":"Y. 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