ArticleThe Journal of experimental medicine2022
Chronic activation of pDCs in autoimmunity is linked to dysregulated ER stress and metabolic responses.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 57 citations in OpenAlex.
- XBP1 signaling from tumor metabolic stress to myeloid driven immunotherapy resistance (Review).International journal of molecular medicine · 2026Review
- Investigation of Cytokine Profiles, the Expression of Genes Involved in Somatic Hypermutation and Peripheral Tolerance, and Their Correlation with Autoantibody Levels in Northern-Thai Immunodeficient Patients Carrying Anti-Interferon-γ Autoantibodies.International journal of molecular sciences · 2026Article
- Reprogramming of the lipid metabolism axis in systemic sclerosis: mechanism analysis and therapeutic potential.Clinical rheumatology · 2026Review
- Stress-driven reprogramming of plasmacytoid dendritic cells in intrahepatic cholangiocarcinoma defines a reversible targetable immunosuppressive state.World journal of surgical oncology · 2026Article
- Reactive oxygen species and metabolic checkpoints shape plasmacytoid dendritic cell fate in infection and autoimmunity.Redox biology · 2026Review
- Role of the IRE1α-XBP1 Axis in IgE-Dependent Activation of Mast Cells.International journal of molecular sciences · 2026Article
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Targeting the UPR with Small Molecules: Emerging Strategies for Immune Regulation.Molecules (Basel, Switzerland) · 2026Review
- Dual-function cytokines as modulators of autophagy: reprogramming inflammatory resolution in severe COVID-19.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Single cell transcriptomics reveals dendritic cell subsets in bovine afferent lymph and immune cell-resolved responses to BCG vaccination.Frontiers in immunology · 2026Article
- Plasmacytoid dendritic cells in systemic and cutaneous lupus erythematosus: an evolving understanding.Frontiers in immunology · 2026Review
- Toll-like receptors in innate immunity and inflammation: from fundamental biology to clinic insights.Immunity & inflammation · 2026Review
- Unveiling biomarkers of telitacicept's efficacy in SLE treatment through proteomics and metabolomics.Frontiers in immunology · 2026Article
- Glycolysis in the tumor microenvironment shapes dendritic cell function and antitumor immunity.Frontiers in immunology · 2026Review
- Glucose metabolic reprogramming in systemic lupus erythematosus and lupus nephritis: theoretical foundations and therapeutic implications.Frontiers in immunology · 2026Review
- The immunoproteasome regulates ILC2 responses by modulating mitochondrial capacity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Escape From X Chromosome Inactivation as a Driver of Plasmacytoid DC Heterogeneity in Health and Disease.Immunological reviews · 2025Review
- Dendritic cell heterogeneity and its role in connective tissue diseases.Inflammation and regeneration · 2025Review
- Identification of a Selective Pharmacologic IRE1/XBP1s Activator with Enhanced Tissue Exposure.ACS chemical biology · 2025Article
- The Inactive X Chromosome: A Genetic Driver of Female-Biased Rheumatic Autoimmune Disorders?European journal of immunology · 2025Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Plasmacytoid dendritic cells (pDCs) chronically produce type I interferon (IFN-I) in autoimmune diseases, including systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). We report that the IRE1α-XBP1 branch of the unfolded protein response (UPR) inhibits IFN-α production by TLR7- or TLR9-activated pDCs. In SSc patients, UPR gene expression was reduced in pDCs, which inversely correlated with IFN-I-stimulated gene expression. CXCL4, a chemokine highly secreted in SSc patients, downregulated IRE1α-XBP1-controlled genes and promoted IFN-α production by pDCs. Mechanistically, IRE1α-XBP1 activation rewired glycolysis to serine biosynthesis by inducing phosphoglycerate dehydrogenase (PHGDH) expression. This process reduced pyruvate access to the tricarboxylic acid (TCA) cycle and blunted mitochondrial ATP generation, which are essential for pDC IFN-I responses. Notably, PHGDH expression was reduced in pDCs from patients with SSc and SLE, and pharmacological blockade of TCA cycle reactions inhibited IFN-I responses in pDCs from these patients. Hence, modulating the IRE1α-XBP1-PHGDH axis may represent a hitherto unexplored strategy for alleviating chronic pDC activation in autoimmune disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.