Projects per year
Abstract
Systemic lupus erythematosus (lupus) is an autoimmune disease characterized by autoantibodies that form immune complexes with self-antigens, which deposit in various tissues, leading to inflammation and disease. The etiology of disease is complex and still not completely elucidated. Dysregulated inflammation is an important disease feature, and the mainstay of lupus treatment still utilizes nonspecific anti-inflammatory drugs. Granulocyte colony-stimulating factor (G-CSF) is a growth, survival, and activation factor for neutrophils and a mobilizer of hematopoietic stem cells, both of which underlie inflammatory responses in lupus. To determine whether G-CSF has a causal role in lupus, we genetically deleted G-CSF from Lyn-deficient mice, an experimental model of lupus nephritis. Lyn−/−G-CSF−/− mice displayed many of the inflammatory features of Lyn-deficient mice; however, they had reduced bone marrow and tissue neutrophils, consistent with G-CSF's role in neutrophil development. Unexpectedly, in comparison to aged Lyn-deficient mice, matched Lyn−/−G-CSF−/− mice maintained neutrophil hyperactivation and exhibited exacerbated numbers of effector memory T cells, augmented autoantibody titers, and worsened lupus nephritis. In humans, serum G-CSF levels were not elevated in patients with lupus or with active renal disease. Thus, these studies suggest that G-CSF is not pathogenic in lupus, and therefore G-CSF blockade is an unsuitable therapeutic avenue.
Original language | English |
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Pages (from-to) | 758-770 |
Number of pages | 13 |
Journal | Immunity, Inflammation and Disease |
Volume | 9 |
Issue number | 3 |
DOIs | |
Publication status | Published - Sept 2021 |
Keywords
- autoimmune disease
- granulocyte colony-stimulating factor
- inflammation
- Lyn tyrosine kinase
- systemic lupus erythematosus
Projects
- 1 Finished
Equipment
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Animal Research Platform (MARP)
Christine Findlay (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility
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FlowCore
Andrew Fryga (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility
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Histology Platform
Camilla Cohen (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility