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Maternal autoantibodies may elicit systemic exaggerated immune responses involving type I interferon (IFN) signalling cascade, yet peripheral circulating immunity in CHB pathogenesis remains poorly understood. To investigate this, we performed single\u2010cell RNA sequencing (scRNA\u2010seq), followed by differential expression gene (DEG) analysis, SCENIC analysis, pseudotime analysis and cell communication analysis, to characterize systemic immune alterations in foetuses with CHB treated with dexamethasone and validated key findings by real\u2010time quantitative PCR (qPCR) and flow cytometry. Compared with controls, CHB foetuses exhibited a markedly activated inflammatory response involving both IFN and NF\u2010\u03baB pathways. Although monocytes showed significant changes in cellular proportions, upregulated DEGs and interferon\u2010stimulated genes, prioritized cellular responses and enhanced intercellular interactions. Notably,\n                    <jats:italic>THBS1+CD14+<\/jats:italic>\n                    monocytes had a pro\u2010inflammatory phenotype with upregulated NLRP3 inflammasome\u2010related genes and maturation toward a pro\u2010inflammatory state, and\n                    <jats:italic>Thbs1<\/jats:italic>\n                    conditional knockout mice showed reduced\n                    <jats:italic>IL\u20101\u03b2<\/jats:italic>\n                    levels in BMDMs. Additionally, dexamethasone\u2010treated monocytes had downregulated\n                    <jats:italic>SOD2<\/jats:italic>\n                    (anti\u2010apoptotic) levels compared to controls, confirmed by qPCR, and flow cytometry verified that dexamethasone promoted monocyte apoptosis. In conclusion, the peripheral immune system in CHB is characterized by innate immune activation driven mainly by monocytes, along with systemic inflammation including IFN signalling.\n                    <jats:italic>THBS1+<\/jats:italic>\n                    \/\n                    <jats:italic>CD14+<\/jats:italic>\n                    monocytes represent a distinct proinflammatory phenotype potentially linked to NLRP3\u2010mediated inflammatory responses.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.71270","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T06:47:09Z","timestamp":1784702829000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single Cell\n                    <scp>RNA<\/scp>\n                    Sequencing Reveals\n                    <i>THBS1<\/i>\n                    +\n                    <i>CD14<\/i>\n                    + Monocyte Modulates Inflammatory Activation via NRLP3\u2010Inflammasome in Congenital Heart Block"],"prefix":"10.1111","volume":"30","author":[{"given":"Sha","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Ministry of Education Key Laboratory of Women and Children's Diseases and Birth Defects, West China Second University Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ministry of Education Key Laboratory of Women and Children's Diseases and Birth Defects, West China Second University Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ministry of Education Key Laboratory of Women and Children's Diseases and Birth Defects, West China Second University 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