Academic Journal
Extrafollicular Tph2-CD11c+CD21- B cell interactions orchestrate immune dysregulation in IgG4-related disease.
| Τίτλος: | Extrafollicular Tph2-CD11c+CD21- B cell interactions orchestrate immune dysregulation in IgG4-related disease. |
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| Συγγραφείς: | Sakamoto H; Department of Otolaryngology and Head and Neck Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan., Kamekura R; Department of Otolaryngology and Head and Neck Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan; Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan. Electronic address: rkameku@sapmed.ac.jp., Takayanagi S; Department of Otolaryngology and Head and Neck Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan., Tanaka A; Department of Otolaryngology and Head and Neck Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan., Yajima R; Department of Otolaryngology and Head and Neck Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan., Yamamoto K; Department of Otolaryngology and Head and Neck Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan., Okuni T; Department of Otolaryngology and Head and Neck Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan., Kurose M; Department of Otolaryngology and Head and Neck Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan., Yamamoto M; Department of Rheumatology and Allergy, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan., Takahashi H; Department of Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan., Ichimiya S; Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan., Takano K; Department of Otolaryngology and Head and Neck Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan. |
| Πηγή: | Allergology international : official journal of the Japanese Society of Allergology [Allergol Int] 2026 Jul; Vol. 75 (3), pp. 463-475. Date of Electronic Publication: 2026 Feb 21. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: England NLM ID: 9616296 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1440-1592 (Electronic) Linking ISSN: 13238930 NLM ISO Abbreviation: Allergol Int Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2015- : London : Elsevier Original Publication: Carlton, Vic., Australia : Blackwell Science, c1996- |
| Ιατρικοί όροι (MeSH): | Immunoglobulin G4-Related Disease*/immunology , Immunoglobulin G4-Related Disease*/metabolism , B-Lymphocytes*/immunology , B-Lymphocytes*/metabolism, Immunoglobulin G/immunology ; Immunoglobulin G/blood ; CD11c Antigen/metabolism ; CD11c Antigen/immunology ; Receptors, Complement 3d/metabolism ; Receptors, Complement 3d/immunology ; T-Lymphocytes, Helper-Inducer/immunology ; Humans ; Male ; Female ; Middle Aged ; Adult |
| Περίληψη: | Background: IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder characterized by IgG4-positive plasma cell infiltration and ectopic lymphoid structure formation. Although glucocorticoids are effective, relapse rates and adverse effects highlight the need for novel therapeutic targets. The immunological basis of IgG4-RD remains incompletely understood. Methods: We analyzed peripheral blood mononuclear cells and inflammatory cells from the affected submandibular glands of patients with IgG4-RD using FACS. We assessed T peripheral helper (Tph) cell subsets and CD11c+CD21- B cells and examined their associations with immunological and clinical parameters. Results: Tph2 cells in peripheral blood and submandibular glands were significantly increased in patients with IgG4-RD, and circulating Tph2 cells expressed granzyme B, indicating their cytotoxic potential. Their frequency correlated positively with serum IgG4, soluble IL-2 receptor levels, plasmablast expansion, eosinophil counts, number of affected organs, and IgG4-RD Responder Index. CD11c+CD21- B cells were also expanded and enriched in IgG4-producing subsets. These cells showed strong correlations with serum IgG4 levels, the IgG4/IgG ratio, and disease activity, but were inversely related to T follicular helper cells. Notably, Tph2 cells exhibited a robust positive correlation with CD11c+CD21- B cells, defining a distinct extrafollicular immune axis. Glucocorticoid treatment reduced Tph2 frequencies in parallel with serum IgG4 decline. Conclusions: This study identifies a novel Tph2-CD11c+CD21- B cell axis driving extrafollicular immune dysregulation in IgG4-RD. Tph2 cells link humoral activation with cytotoxicity, and CD11c+CD21- B cells serve as producers of IgG4 associated with disease severity. Targeting this axis may provide therapeutic strategies for refractory or relapsing IgG4-RD beyond glucocorticoids. (Copyright © 2026 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.) |
| Competing Interests: | Conflict of interest The authors have no conflict of interest to declare. |
| Contributed Indexing: | Keywords: CD11c(+)CD21(-) B cells; Ectopic lymphoid structures; Extrafollicular immune response; IgG4-related disease; T peripheral helper 2 (Tph2) cells |
| Substance Nomenclature: | 0 (Immunoglobulin G) 0 (CD11c Antigen) 0 (Receptors, Complement 3d) |
| Entry Date(s): | Date Created: 20260221 Date Completed: 20260613 Latest Revision: 20260613 |
| Update Code: | 20260615 |
| DOI: | 10.1016/j.alit.2026.01.005 |
| PMID: | 41723099 |
| Βάση Δεδομένων: | MEDLINE |
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