Atopic dermatitis (AD) presents significant therapeutic challenges due to its poorly understood etiology. Eosinophilia, a hallmark of allergic inflammation, is implicated in AD pathogenesis. Interleukin-10 (IL-10)-producing regulatory B (Breg) cells exhibit potent anti-inflammatory effects. However, their role in controlling AD-related eosinophilia is not well understood. To investigate the impact of eosinophils on AD, we employed IL-5Rα-deficient (Il5ra) mice, which lack functional eosinophils. Induction of AD in these mice resulted in attenuated disease symptoms, underscoring the critical role of eosinophils in AD development. Additionally, the adoptive transfer of purified Breg cells into mice with AD significantly alleviated disease severity. Mechanistic studies revealed that IL-10 produced by Breg cells directly inhibits eosinophil activation and infiltration into the skin. In vitro experiments further confirmed that Breg cells inhibited eosinophil peroxidase secretion in an IL-10-dependent manner. Our collective findings demonstrate that IL-10 from Breg cells alleviates AD by suppressing eosinophil activation and tissue infiltration. This study elucidates a novel regulatory mechanism of Breg cells, providing a foundation for future Breg-mediated therapeutic strategies for AD.
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http://dx.doi.org/10.1038/s41598-024-68660-9 | DOI Listing |
Am J Reprod Immunol
February 2025
Department of Anthropology, University of California, Los Angeles, California, USA.
Problem: Regulatory B-cells (Bregs, CD19CD24CD38) are a specialized B-cell subset that suppresses immune responses and potentially contribute to the maintenance of an immune-privileged environment for fetal development during pregnancy. However, little is known about the surrounding immunological environment of Bregs in gestational physiology. The relationship of regulatory T-cells (Tregs, CD4CD25CD127FoxP3) to Bregs in coordinating immunoregulation during pregnancy is unknown.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
Introduction: Mycophenolate mofetil (MMF) is an immunosuppressive drug administered in the management of both autoimmune diseases and organ transplantation. The main aims of the study were: (a) to obtain information regarding the safety of using MMF in respect of its effect on normal T and B cells in lymphoid tissues; (b) to investigate whether the generation of inducible Foxp3-expressing regulatory T cells (Treg) might constitute additional mechanisms underlying the immunosuppressive properties of MMF.
Methods: The effect of MMF ( studies) and its active metabolite, mycophenolic acid, ( studies) on murine CD4 and CD8 T cells as well as B cells was determined, regarding: (a) absolute count, proliferation and apoptosis of these cells ( studies); (b) absolute count of these cells in the head and neck lymph nodes, mesenteric lymph nodes and the spleen ( studies).
Am J Clin Exp Immunol
December 2024
Department of Surgery, Medical Faculty, Trakia University Stara Zagora, Bulgria.
Tertiary lymphoid structures (TLS), formerly recognized as Crohn's-like structures, serve as crucial biomarkers for evaluating the progression of colorectal cancer (CRC). Understanding their spatial distribution, cellular composition, and interactions within CRC is paramount for comprehending the immune response in the tumor microenvironment (TME). TLS are comprised of a T-cellular compartment and a B-cellular compartment, the latter encompassing follicular dendritic cells (FDCs), high endothelial venules (HEVs), and lymphatic vessels.
View Article and Find Full Text PDFImmunology
January 2025
Institute of Genetic and Biomedical Research (IRGB), Italian National Research Council (CNR), Monserrato, Sardinia, Italy.
The TYK2:p.Pro1104Ala (rs34536443) hypomorph variant has been associated with protection against numerous autoimmune disorders. Thus, its mechanism of action becomes of great interest.
View Article and Find Full Text PDFNat Commun
January 2025
Laboratory of Genome Diversification & Integrity, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125, Berlin, Germany.
The establishment of protective immune responses relies on the ability of terminally differentiated B cells to secrete a broad variety of antigen-specific antibodies with different effector functions. RIF1 is a multifunctional protein that promotes antibody isotype diversification via its DNA end protection activity during class switch recombination. In this study, we showed that RIF1 ablation resulted in increased plasmablast formation ex vivo and enhanced terminal differentiation into plasma cells upon immunization.
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