ArticleProceedings of the National Academy of Sciences of the United States of America2021
IL-27-producing B-1a cells suppress neuroinflammation and CNS autoimmune diseases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 66 citations in OpenAlex.
- B cells in cancer: functions, mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Phosphorylated TYK2 orchestrates the pathogenic program of CD4 + T cells in the development of CNS autoimmunity.Journal of neuroinflammation · 2026Article
- Review
- Programmed death-ligand 1 on ex vivo-expanded toll-like-receptor-Bregs prevents allograft rejection by Breg viability promotion, CD4American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- A distinct TCRiScience · 2026Article
- Reframing IL-27: a central regulator of CD8Trends in immunology · 2026Review
- The role and mechanism of IL‑35 in myasthenia gravis (Review).International journal of molecular medicine · 2026Review
- IL-35 enhances IL-10⁺ breg-mediated immunoregulation and attenuates inflammation and fibrosis in systemic sclerosis.Arthritis research & therapy · 2026Article
- A decoy oligodeoxynucleotide favors the differentiation of CpG ODN-induced B cells into IL-10-producing Breg-like cells over plasma cells by restoring IRF4/IRF8 imbalance.Cellular and molecular life sciences : CMLS · 2026Article
- Shifting the paradigm in bipolar disorder: moving beyond conventional inflammatory markers to novel EBI3-containing heterodimeric cytokines.Frontiers in psychiatry · 2026Article
- Regulatory B cell CCL3 competency promotes disease resolution and oligodendrogenesis in experimental autoimmune encephalomyelitis.Communications biology · 2025Article
- Ligand-receptor interactions induce and mediate regulatory functions of BATF3Science advances · 2025Article
- Neuroinflammation and Amyotrophic Lateral Sclerosis: Recent Advances in Anti-Inflammatory Cytokines as Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Revealing the role of regulatory b cells in cancer: development, function and treatment significance.Cancer immunology, immunotherapy : CII · 2025Review
- The role of BATF in immune cell differentiation and autoimmune diseases.Biomarker research · 2025Review
- The half-century odyssey of regulatory B cells: from Breg discovery to emerging frontiers.Frontiers in immunology · 2025Review
- The mCell death and differentiation · 2025Article
- Interleukin 35-producing B cells prolong the survival of GVHD mice by secreting exosomes with membrane-bound IL-35 and upregulating PD-1/LAG-3 checkpoint proteins.Theranostics · 2025Article
- IL-6/IL-12 superfamily of cytokines and regulatory lymphocytes play critical roles in the etiology and suppression of CNS autoimmune diseases.Frontiers in immunology · 2025Review
- Heterogeneity of regulatory B cells in autoimmune diseases: implications for immune equilibrium and therapeutic strategies.Immunotherapy advances · 2025Review
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Regulatory B cells (Breg cells) that secrete IL-10 or IL-35 (i35-Breg) play key roles in regulating immunity in tumor microenvironment or during autoimmune and infectious diseases. Thus, loss of Breg function is implicated in development of autoimmune diseases while aberrant elevation of Breg prevents sterilizing immunity, exacerbates infectious diseases, and promotes cancer metastasis. Breg cells identified thus far are largely antigen-specific and derive mainly from B2-lymphocyte lineage. Here, we describe an innate-like IL-27-producing natural regulatory B-1a cell (i27-Breg) in peritoneal cavity and human umbilical cord blood. i27-Bregs accumulate in CNS and lymphoid tissues during neuroinflammation and confers protection against CNS autoimmune disease. i27-Breg immunotherapy ameliorated encephalomyelitis and uveitis through up-regulation of inhibitory receptors (Lag3, PD-1), suppression of Th17/Th1 responses, and propagating inhibitory signals that convert conventional B cells to regulatory lymphocytes that secrete IL-10 and/or IL-35 in eye, brain, or spinal cord. Furthermore, i27-Breg proliferates in vivo and sustains IL-27 secretion in CNS and lymphoid tissues, a therapeutic advantage over administering biologics (IL-10, IL-35) that are rapidly cleared in vivo. Mutant mice lacking irf4 in B cells exhibit exaggerated increase of i27-Bregs with few i35-Bregs, while mice with loss of irf8 in B cells have abundance of i35-Bregs but defective in generating i27-Bregs, identifying IRF8/BATF and IRF4/BATF axis in skewing B cell differentiation toward i27-Breg and i35-Breg developmental programs, respectively. Consistent with its developmental origin, disease suppression by innate i27-Bregs is neither antigen-specific nor disease-specific, suggesting that i27-Breg would be effective immunotherapy for a wide spectrum of autoimmune diseases.
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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.