{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T06:12:14Z","timestamp":1778825534089,"version":"3.51.4"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"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>Background<\/jats:title>\n                    <jats:p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by immune cell dysfunction. The endomembrane system, consisting of the endoplasmic reticulum (ER) and Golgi apparatus (GA), plays a central role in protein synthesis and trafficking. However, the regulatory architecture of the ER-Golgi axis in RA immune cells remains incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed an integrative multi-omics analysis of peripheral blood mononuclear cells (PBMCs) from 96 RA patients and 90 healthy controls (HCs). Proteomic data were obtained from a previously published study from our research group, and transcriptomic data were retrieved from the GEO database (GSE17755). Protein-protein interaction (PPI) networks were constructed using STRING and Cytoscape. Kinase activity and related signaling molecules were identified based on the functional annotations of differentially expressed proteins and phosphoproteins. Upstream transcription factor (TF) regulatory networks were built through integration with hTFtarget. Drug candidates were screened using the DSigDB database.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>RA immune cells exhibited coordinated dysregulation of the ER-Golgi axis. Proteomics revealed downregulation of vesicular transport components (RAB1A, SEC16A) and upregulation of ER stress-related proteins (DNAJC3, SERPINH1). Phosphoproteomics identified 122 differentially phosphorylated sites, including novel hypophosphorylation of SEC16A (S1305\/S1356) and decreased phosphorylation of PRKCD at T507, T295, and S664, suggesting altered PRKCD-related signaling in RA immune cells. PPI network analysis highlighted RPS3 as a dual hub linking translation and inflammatory signaling. Upstream regulatory analysis identified PML, STAT1, CBFB, and RAD21 as potential TFs, while AKT1-CK2-PRKD and TBK1-IKBKB constituted major kinase hubs. These findings indicate coordinated alterations in vesicular transport, ER stress-related processes, and inflammatory signaling in RA immune cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This integrative multi-omics analysis characterizes coordinated alterations of the ER-Golgi axis in RA immune cells and highlights candidate regulatory nodes, including SEC16A phosphorylation sites, RPS3, and major kinase hubs. As a hypothesis-generating study, these findings provide a systems-level framework for understanding how endomembrane dysregulation may be associated with sustained immune activation in RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1811568","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T05:42:17Z","timestamp":1778823737000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["ER-Golgi dysfunction and vesicular transport alterations in rheumatoid arthritis immune cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Yangna","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital, Jinan University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Peking University Shenzhen Hospital","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenxi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital, Jinan University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanna","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital, Jinan University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lianghong","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital, Jinan University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongzhou","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Shenzhen People\u2019s 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Shenzhen Autoimmune Disease Engineering Research Center, Shenzhen People\u2019s Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University)","place":["Shenzhen, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhipeng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Autoimmune Disease Precision Medicine Engineering Research Center, Shenzhen Autoimmune Disease Engineering Research Center, Shenzhen People\u2019s Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University)","place":["Shenzhen, China"]},{"name":"Clinical Medical Research Center, Shenzhen People\u2019s Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University)","place":["Shenzhen, 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