Abstract
Impact of type I IFN signaling on B cell pathogenicity in a mouse model of early Sjögren’s disease
The Journal of immunology (1950), Vol.210(1_Supplement), p.247.02
05/01/2023
DOI: 10.4049/jimmunol.210.Supp.247.02
Abstract
Abstract Sjögren’s disease is a chronic autoimmune disease characterized by focal inflammation of the lacrimal and salivary glands. NOD mice spontaneously develop lacrimal gland inflammation by 5–6 weeks. As disease progresses, B cells accumulate in the glands and produce antibodies resulting in glandular dysfunction. Disruption of the type I interferon (IFN) signaling pathway protects NOD mice from developing lacrimal gland disease. While the impact of B cells later in disease has been well-characterized, the role of B cells in early disease development has not been defined. Here, we performed gene expression studies, adoptive transfers, and spectral flow cytometry to define the phenotype of B cell subsets and the potential role of type I IFN signaling in lacrimal gland autoimmunity. Gene expression studies demonstrated that genes associated with B cell receptor signaling, lymphocyte trafficking and antigen presentation were upregulated at 10 weeks compared to 6 weeks. Flow cytometry of the lacrimal glands showed that most early B cells express IFNAR1. Adoptive transfer studies demonstrated decreased disease when donor cells lacked IFNAR1 expression compared to WT donor cells, but this difference was abrogated when magnetically purified T cells were transferred suggesting a type I IFN dependent pathogenic role on a non-T cell population. In vitro studies show that B cell phenotype can be shaped by IFNα in a dose dependent manner. Type l IFN signaling drives the development of lacrimal gland autoimmunity in NOD mice. Type l IFN signaling shapes B cell phenotype and function in early lacrimal gland disease. Ongoing in vivo studies will interrogate the impact of IFNAR1 expression on B cell trafficking to the lacrimal glands. Supported by grants from NIH (R01 EY027731)
Details
- Title: Subtitle
- Impact of type I IFN signaling on B cell pathogenicity in a mouse model of early Sjögren’s disease
- Creators
- Merri-Grace AllredScott M Lieberman
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.210(1_Supplement), p.247.02
- DOI
- 10.4049/jimmunol.210.Supp.247.02
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2023
- Academic Unit
- Stead Family Department of Pediatrics; Rheumatology, Allergy, and Immunology
- Record Identifier
- 9984455615702771
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