Dissecting the Genetics and Function of CD5+ B and invariant NKT cells using Congenic Lupus-Prone Mouse Strains
Year: 2017
Type: dissertation
Abstract: Systemic lupus erythematosus (SLE) is a complex multisystem autoimmune disorder characterized by the production of antibodies to nuclear antigens. Congenic strains derived from lupus-prone mice have been extremely useful in determining the pathogenesis of this condition. These mice, which harbor selected genetic elements containing susceptibility loci, can be used to identify key pathways and immune networks involved in disease initiation and progression. Alternatively, these same models can be used to identify the role of suppressive regulatory cells involved in preventing disease. In this thesis, the role and function of CD5+ and invariant Natural Killer T (iNKT) innate lymphocytes were investigated in the suppression of disease in New Zealand Black lupus-prone congenic mice. Through adoptive transfer and knockout experiments, CD5+ B cells, but not iNKT cells, were shown to suppress autoimmunity by inhibiting the frequencies of proinflammatory T cell subsets. As these CD5+ B cells secreted IL-10, which has been shown previously to suppress disease, the role of this cytokine was further investigated through knockout experiments that highlighted its critical role in maintaining CD5+ B, iNKT, and Natural Killer cell homeostasis. Finally, the immunogenetic basis of impaired iNKT cell function in the congenic mouse strains was investigated, revealing a critical role for Ly108 in iNKT cell development and function. Collectively, these findings highlight the role of CD5+ B cells and iNKT cells in SLE pathogenesis and demonstrate the power of congenic animals to dissect the genetic basis of disease.
Source: TSpace (University of Toronto)
Author: Yuriy Baglaenko
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2620889642