Ets1 Controls the Development of B Cell Autoimmune Responses in a Cell-Intrinsic Manner
| Autor: | Lee Ann Garrett-Sinha, Justin Dalton, Alifa Stith, Katherine Sortino, Sarah Metcalfe, David Goich, Eric C. Svensson, Alex Sunshine |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cell type T cell Immunology Cell Autoimmunity Antigen-Antibody Complex Biology CD8-Positive T-Lymphocytes medicine.disease_cause Kidney Lymphocyte Activation Article Proto-Oncogene Protein c-ets-1 03 medical and health sciences Gene Knockout Techniques Mice 0302 clinical medicine ETS1 medicine Immunology and Allergy Animals B cell Alleles 030304 developmental biology Autoantibodies Mice Knockout 0303 health sciences B-Lymphocytes Systemic lupus erythematosus Autoantibody Cell Differentiation General Medicine medicine.disease Molecular biology 3. Good health Mice Inbred C57BL medicine.anatomical_structure Phenotype Immunoglobulin M Immunoglobulin G 030215 immunology |
| Zdroj: | ImmunoHorizons |
| ISSN: | 2573-7732 |
| Popis: | Ets1 is emerging as a key transcription factor that is required to prevent autoimmunity in mice and humans. Ets1 is expressed in both B and T cells, and mice lacking Ets1 are characterized by excess B and T cell activation, leading to enhanced formation of Ab-secreting cells and high titers of autoantibodies. In humans, genome-wide association studies have detected associations of single nucleotide polymorphisms in the human ETS1 gene with autoimmune diseases, including lupus. An increased fraction of CD4+ T cells from Ets1−/− mice have an activated effector-memory phenotype, and there are aberrations in differentiation that contribute to the autoimmune phenotype. In vitro studies of B cells suggest that Ets1 may have B cell–intrinsic effects as well. To confirm B cell–intrinsic roles for Ets1, we crossed CD19-Cre mice to mice with a floxed allele of Ets1. Mice with a B cell–specific deletion of Ets1 show increases in B cell activation, numbers of Ab-secreting cells, and levels of autoantibodies, despite the fact that T cells are normal. However, when compared with conventional Ets1 knockout mice, mice with B cell–specific loss of Ets1 have a significantly milder phenotype. These results demonstrate that Ets1 is required in B cells to prevent autoimmune responses but that loss of Ets1 activity in other cell types is required for maximal autoimmune phenotypes. |
| Databáze: | OpenAIRE |
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