B Cell ADAM10 Controls Murine Lupus Progression through Regulation of the ICOS:ICOS Ligand Axis
Autor: | Daniel H. Conrad, Rebecca K. Martin, Jessica L. Wimberly, Joseph C. Lownik |
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Rok vydání: | 2019 |
Předmět: |
T cell
Immunology Autoimmunity Context (language use) medicine.disease_cause Article Inducible T-Cell Co-Stimulator Protein ADAM10 Protein Inducible T-Cell Co-Stimulator Ligand Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Lupus Erythematosus Systemic Immunology and Allergy B cell Autoantibodies Cell Proliferation Mice Knockout B-Lymphocytes Systemic lupus erythematosus Chemistry Membrane Proteins Germinal center medicine.disease Immunity Humoral ICOS LIGAND Disease Models Animal MicroRNAs medicine.anatomical_structure Gene Expression Regulation Humoral immunity Disease Progression Amyloid Precursor Protein Secretases 030215 immunology |
Zdroj: | The Journal of Immunology. 202:664-674 |
ISSN: | 1550-6606 0022-1767 |
Popis: | The role of ICOS and its ligand (ICOSL) have both been shown to be essential for proper humoral responses as well as autoimmune Ab development in mouse models of lupus. In this paper, we report a specific role for the metalloprotease ADAM10 on B cells in regulating both ICOSL and ICOS in a mouse model of increased humoral immunity using B6mir146a−/− mice and a model of lymphoproliferative disease using the well-characterized lpr model. B6lpr mice lacking ADAM10 on B cells (A10Blpr) have decreased nodal proliferation and T cell accumulation compared with control B6lpr mice. Additionally, A10Blpr mice have a drastic reduction in autoimmune anti-dsDNA Ab production. In line with this, we found a significant reduction in follicular helper T cells and germinal center B cells in these mice. We also show that lymphoproliferation in this model is closely tied to elevated ICOS levels and decreased ICOSL levels. Overall, our data not only show a role of B cell ADAM10 in control autoimmunity but also increase our understanding of the regulation of ICOS and ICOSL in the context of autoimmunity. |
Databáze: | OpenAIRE |
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