Abstract
IL-27 signaling contributes to pathogenic T cells in a mouse model of Sjögren’s
The Journal of immunology (1950), Vol.208(1_Supplement), pp.44-44.02
05/01/2022
DOI: 10.4049/jimmunol.208.Supp.44.02
Abstract
Abstract Sjögren’s is an autoimmune disease with limited therapies due to an incomplete understanding of the immunological mechanisms that contribute to disease. Non-obese diabetic (NOD) mice spontaneously develop lacrimal gland inflammation dominated by early T cell infiltration, mirroring human disease. IL-27 is elevated in serum and saliva of Sjögren’s patients and is required for disease development in NOD mice. Here, we define the requirements of IL-27 signaling in effector T cell subsets in the context of lacrimal gland autoimmunity. We utilized IL-27Rα KO NOD mice and an adoptive transfer model to determine which T cell subsets require IL-27 signaling to mediate lacrimal gland inflammation in NOD-SCID recipients. Both CD4 and CD8 T cells require IL-27Rα to transfer disease. Through co-transferring different combinations of KO and WT effector T cells, we found significantly decreased disease development when CD4 effector T cells did not express IL-27Rα. The role of IL-27 signaling in CD4 T cells is further supported by co-transfers of bulk lymphocytes from WT and KO mice which implicate IL-27 in driving the imbalance of CD4 effector T cells to Tregs in lacrimal glands. Additionally, Nanostring analyses performed on whole lacrimal glands from WT and KO mice support a role for IL-27 in driving pathogenic T cell infiltration. Together, these data demonstrate a pathogenic role for IL-27 in the T cell dysregulation in Sjögren’s. Supported by grants from NIH (2T32 AI007485, DK121747 and EY027731)
Details
- Title: Subtitle
- IL-27 signaling contributes to pathogenic T cells in a mouse model of Sjögren’s
- Creators
- Ivy L DebreceniYi-Guang ChenScott M Lieberman
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.208(1_Supplement), pp.44-44.02
- DOI
- 10.4049/jimmunol.208.Supp.44.02
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2022
- Academic Unit
- Stead Family Department of Pediatrics; Rheumatology, Allergy, and Immunology
- Record Identifier
- 9984354504702771
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