{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T00:47:02Z","timestamp":1793234822526,"version":"4.5.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"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":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To characterize shared immune-associated programs between sepsis and systemic lupus erythematosus (SLE), define the cellular context of prioritized candidate genes, and functionally evaluate SIGLEC1 in macrophage inflammatory responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Public transcriptomic datasets were analyzed to identify common differentially expressed genes using the limma package. Shared candidate genes were characterized using protein-protein interaction and enrichment analyses, and prioritized candidates were subsequently selected using an integrated multi-dimensional evidence framework combining discovery-stage differential expression and orthogonal supporting evidence.Single-cell RNA sequencing (scRNA-seq) analysis was performed on five in-house samples (normal, SIRS, and sepsis) and integrated with external datasets (GSE167363 for sepsis; GSE162577 and GSE136035 for SLE) using Harmony. Cell-type distribution, gene expression patterns, and pathway activity were systematically evaluated. Immune infiltration, protein-level association, and discriminatory performance between disease cohorts and healthy controls was further assessed using external cohorts. Finally, qPCR validation and SIGLEC1 loss-of-function experiments were performed in THP-1-derived macrophages, followed by assessment of inflammatory cytokine production by ELISA and macrophage activation phenotype by flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 49 shared candidate genes were identified in the initial discovery analysis. Using an integrated prioritization framework, TRIM25 and SIGLEC1 ranked third and fourth, respectively, among the 49 candidates and were selected for further investigation based on their high overall prioritization and complementary evidence profiles.Subsequent analyses revealed disease- and cohort-dependent expression patterns of these genes. Single-cell analysis indicated that SIGLEC1 expression was primarily confined to monocyte\/macrophage populations, while TRIM25 was more widely expressed among various immune cells. Sepsis samples were characterized by innate immune cell enrichment, while SLE samples showed increased adaptive immune cell proportions. Pathway analysis demonstrated shared activation of inflammatory signaling but distinct immune programs between diseases. Both genes exhibited potential discriminatory capacity between disease cohorts and healthy controls, while experimental validation supported the inducible expression patterns of both genes under disease-associated stimulation. Furthermore, SIGLEC1 knockdown attenuated LPS-induced IL-6 and TNF-\u03b1 production and reduced the CD86-positive macrophage phenotype, providing functional evidence for its involvement in macrophage inflammatory responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SIGLEC1 and TRIM25 are context-dependent immune signatures in sepsis and SLE, with loss-of-function evidence supporting SIGLEC1 in macrophage inflammatory responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1892194","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:22:49Z","timestamp":1788412969000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Single-cell profiling reveals context-dependent immune regulation shared by sepsis and systemic lupus 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