Academic Journal
Elevated IL-10 is Linked With the Expansion of T-bethighCD21low B Cells in Patients With Common Variable Immunodeficiency.
| Τίτλος: | Elevated IL-10 is Linked With the Expansion of T-bethighCD21low B Cells in Patients With Common Variable Immunodeficiency. |
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| Συγγραφείς: | Cousin V; Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Schaenzlestrasse 1, 79104, Freiburg, Germany.; Spemann Graduate School of Biology and Medicine, University of Freiburg, Freiburg, Germany., Graumann A; Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Geiger V; Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Faculty of Biology, University of Freiburg, Schaenzlestrasse 1, 79104, Freiburg, Germany., Sökler D; Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Bez P; Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Department of Medicine (DIMED), University of Padova, Padua, Italy., Gutenberger S; Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Glaser C; Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Andrieux G; Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Boerries M; Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between, DKFZ and Medical Center - University of Freiburg, Freiburg, Germany., Frye BC; Clinic for Pneumology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany., Zissel G; Clinic for Pneumology, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany., Calvillo CL; Epigenetics and Immune Disease Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, 08916, Barcelona, Spain., Rodriguez-Ubreva J; Epigenetics and Immune Disease Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, 08916, Barcelona, Spain., Ballestar E; Epigenetics and Immune Disease Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, 08916, Barcelona, Spain.; Epigenetics in Inflammatory and Metabolic Diseases Laboratory, Health Science Center (HSC), East China Normal University (ECNU), Shanghai, China., Hauck F; Division of Pediatric Immunology and Rheumatology, Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität (LMU), Munich, Germany., Voll RE; Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Chevalier N; Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Keller B; Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Warnatz K; Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. klaus.warnatz@uniklinik-freiburg.de.; Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. klaus.warnatz@uniklinik-freiburg.de. |
| Πηγή: | Journal of clinical immunology [J Clin Immunol] 2026 Aug 15; Vol. 46 (1). Date of Electronic Publication: 2026 Aug 15. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Springer Country of Publication: Netherlands NLM ID: 8102137 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-2592 (Electronic) Linking ISSN: 02719142 NLM ISO Abbreviation: J Clin Immunol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Springer Original Publication: New York : Plenum, c1981- |
| Ιατρικοί όροι (MeSH): | Interleukin-10*/blood , Interleukin-10*/metabolism , Common Variable Immunodeficiency*/immunology , Common Variable Immunodeficiency*/metabolism , B-Lymphocytes*/immunology , B-Lymphocytes*/metabolism, Receptors, Complement 3d/metabolism ; Cell Differentiation/immunology ; STAT3 Transcription Factor/metabolism ; Interleukins/metabolism ; Lymphocyte Activation/immunology ; B-Lymphocyte Subsets/immunology ; Humans ; Female ; Male ; Interleukin-21 ; Signal Transduction ; Adult |
| Περίληψη: | Common variable immunodeficiency (CVID) is frequently complicated by autoimmune and inflammatory manifestations associated with profound immune dysregulation (CVIDc), including expansion of T-bethighCD21low B cells (CD21low B cells). Elevated serum IL-10 levels have repeatedly been reported in CVIDc, yet their relationship to CD21low B-cell differentiation remains unclear. In this study, we determined a significant correlation between increased serum IL-10 levels and frequency of circulating CD21low B cells, particularly marked in CVIDc patients. Transcriptomic and protein analyses identified multiple cellular sources of IL-10 in CVID, including monocytes, T cells, and a subset of CD21low B cells in peripheral blood and inflamed tissues. CD21low B cells expressed elevated levels of IL-10 receptor subunits and displayed intact IL-10-induced STAT3 signaling, indicating preserved responsiveness to IL-10. Functionally, IL-10 alone neither induced CD21low B-cell differentiation nor inhibited IFN-γ-driven polarization. However, in vitro differentiation assays showed that IL-10 can substitute for IL-21 during CD40L/T cell-dependent differentiation of CD21low-like B cells and promote their survival in vitro. These findings suggest that IL-10 may support the expansion and persistence of CD21low B cells at inflammatory sites. Collectively, our data identify IL-10 as a component of the inflammatory environment associated with CD21low B-cell expansion and suggest that IL-10 can functionally replace IL-21 during their differentiation and promote their survival in CVID-associated immune dysregulation. (© 2026. The Author(s).) |
| Competing Interests: | Declarations. Conflicts of interest: The authors declare no conflicts of interests. |
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| Contributed Indexing: | Keywords: B-cell differentiation; CD21low B cells; Common variable immunodeficiency (CVID); IL-10; Immune dysregulation; Survival; TbethighCD21low B cells; Type 1 inflammation |
| Substance Nomenclature: | 130068-27-8 (Interleukin-10) 0 (Receptors, Complement 3d) MKM3CA6LT1 (Interleukin-21) 0 (STAT3 Transcription Factor) 0 (Interleukins) 0 (IL10 protein, human) |
| Entry Date(s): | Date Created: 20260815 Date Completed: 20260815 Latest Revision: 20260818 |
| Update Code: | 20260818 |
| PubMed Central ID: | PMC13477453 |
| DOI: | 10.1007/s10875-026-02058-2 |
| PMID: | 42603226 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1573-2592 |
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| DOI: | 10.1007/s10875-026-02058-2 |