{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:27:22Z","timestamp":1777609642692,"version":"3.51.4"},"reference-count":40,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Skin inflammation and immune regulation have been suggested to be associated with allergic contact dermatitis (ACD) progression, but whether the system\u2019s immune regulation is a cause or a potential mechanism is still unknown. This study aims to assess the upstream and downstream of systemic immune factors on ACD within a bidirectional Mendelian-randomization design. A bidirectional two-sample MR analysis was employed to implement the results from genome-wide association studies for 52 system immune factors and ACD. Genetic associations with systemic immune factors and ACD were obtained from the IEU Open GWAS project database. The inverse-variance weighted (IVW) method was adopted as the primary MR analysis, MR-Egger, weighted median, MR-pleiotropy residual sum, and outlier (MR-PRESSO) was also used as the sensitivity analyses. Only Tumor necrosis factor ligand superfamily member 11 (TNFS11) from among 52 systemic immune factors was associated with a protective effect of ACD. However, ACD was associated with a decrease in Interleukin-9 (IL9) and an increase in C-X-C motif chemokine 1 (GRO\u03b1), Tumor necrosis factor ligand superfamily member 10 (TRAIL), C4, and complement factor B of the assessed systemic immune factors. This study identified TNFS11 as the upstream regulator and IL9, GRO\u03b1, TRAIL, C4, and complement factor B as the downstream regulator of ACD, providing opportunities for new therapeutic exploitation of ACD. Nonetheless, these associations of systemic immune factors need to be verified in vivo.<\/jats:p>","DOI":"10.3390\/ijms251910436","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T07:49:24Z","timestamp":1727423364000},"page":"10436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Systemic Immune Factors and Risk of Allergic Contact Dermatitis: A Bidirectional Mendelian Randomization Study"],"prefix":"10.3390","volume":"25","author":[{"given":"Yingxin","family":"Long","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenzhang","family":"Dai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kexin","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8854-5184","authenticated-orcid":false,"given":"Yuan","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anqi","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziwei","family":"Lai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junlin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lipeng","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Nie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.cell.2010.02.043","article-title":"Anti-inflammatory Agents: Present and 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