{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:04:47Z","timestamp":1783919087225,"version":"3.55.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["25ZR1402319"],"award-info":[{"award-number":["25ZR1402319"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32030043"],"award-info":[{"award-number":["32030043"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Asthma remains a heterogeneous inflammatory airway disease, and current therapies, including biologics, benefit only selected patient subsets. We aimed to identify genetically supported therapeutic targets with clear mechanistic and translational relevance in asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated cis-eQTL and cis-pQTL instruments for 585 druggable genes with asthma genome-wide association data from FinnGen, EBI, and UK Biobank, comprising more than 1.1 million participants in total, using Mendelian randomization, colocalization, and SMR\/HEIDI analyses. We then combined cell-type-specific single-cell eQTL Mendelian randomization with lung single-cell RNA sequencing from a house dust mite mouse model and public human and cynomolgus monkey single-cell datasets to define the cellular context of the prioritized signal. Phenome-wide association analysis and Connectivity Map screening were used to assess target specificity and nominate candidate compounds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CD83 emerged as the most consistently supported candidate across the genetic prioritization pipeline. Higher genetically predicted CD83 expression showed a consistent risk-increasing association across independent cohorts, and protein-level analyses together with colocalization provided convergent support for CD83 as the prioritized gene at this locus. Mechanistically, integrating cell-type-specific human genetics with cross-species single-cell transcriptomics localized the signal to antigen-presenting cells, particularly memory B cells and dendritic cells. Across human, mouse, and monkey datasets, CD83-positive antigen-presenting cells were consistently enriched for MHCII antigen-presentation and T-cell activation programs following allergen challenge. Phenome-wide analyses did not identify major genome-wide significant associations outside the asthma signal, and signature-reversal analysis highlighted hydroxyfasudil and prunetin as candidate compounds for further evaluation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings prioritize CD83 in antigen-presenting cells as a genetically supported candidate therapeutic target in asthma. More broadly, they provide a translational framework linking human causal genetics to cell-specific mechanism and therapeutic nomination, and support direct CD83 perturbation studies in airway inflammation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1859076","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T04:23:09Z","timestamp":1783916589000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic and cross-species single-cell analyses prioritize CD83 in antigen-presenting cells as a candidate therapeutic target in asthma"],"prefix":"10.3389","volume":"17","author":[{"given":"Guojun","family":"Qian","sequence":"first","affiliation":[{"name":"Key Laboratory of Anesthesiology (Shanghai Jiao Tong University, Ministry of Education), Department of Anesthesiology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, 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