Abstract
Elucidating the role of IL-27 in Sjögren disease-like autoimmunity in the non-obese diabetic mouse model
The Journal of immunology (1950), Vol.206(1_Supplement), pp.61-61.01
05/01/2021
DOI: 10.4049/jimmunol.206.Supp.61.01
Abstract
Abstract Sjögren’s is an autoimmune disease targeting lacrimal and salivary glands leading to debilitating ocular and oral complications. Lack of understanding of the immunopathogenic mechanisms of disease has hindered development of effective therapies. Non-obese diabetic (NOD) mice spontaneously develop gland inflammation with features similar to humans providing a model to study immune signals that drive this autoimmune process. IL-27 is elevated in serum and saliva of Sjögren’s patients and is required for disease development in NOD mice. However, the mechanisms by which IL-27 contributes to Sjögren’s is not fully elucidated. Here, we define the requirements of IL-27 signaling in effector T cell subsets in the context of lacrimal gland autoimmunity. IL-27 is a heterodimeric cytokine (EBI3 + p28) and binds a heterodimeric receptor (gp130 + IL-27Rα). IL-27Rα is expressed on CD8 and CD4 T cells, and both T cell subsets play pathogenic roles in lacrimal gland disease development. We utilized IL-27 KO and IL-27Rα KO NOD mice and an adoptive transfer model, to determine which T cell subsets required intact IL-27 signaling to mediate lacrimal gland inflammation in NOD-SCID recipient mice. Neither CD4 nor CD8 T cells sort-purified from IL-27Rα KO donors transferred disease. In contrast, while CD4 effector T cells from IL-27 KO NOD mice transferred disease, IL-27 KO CD8 T cells did not. Together these data demonstrate a T cell-intrinsic requirement for IL-27 signaling in both effector T cells subsets and suggest that CD8 T cells may also produce IL-27 to drive lacrimal gland inflammation. Flow cytometric and gene expression analyses to further define the immunological pathways driven by IL-27 in the context of lacrimal gland autoimmunity are underway.
Details
- Title: Subtitle
- Elucidating the role of IL-27 in Sjögren disease-like autoimmunity in the non-obese diabetic mouse model
- Creators
- Ivy L Debreceni - University of IowaYi-Guang Chen - Medical College of WisconsinScott M Lieberman - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.206(1_Supplement), pp.61-61.01
- DOI
- 10.4049/jimmunol.206.Supp.61.01
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2021
- Academic Unit
- Stead Family Department of Pediatrics; Rheumatology, Allergy, and Immunology
- Record Identifier
- 9984410790102771
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