Elucidating the pathogenic role of IL-27 in lacrimal gland autoimmunity in the nonobese diabetic mouse model of Sjögren’s Disease

Sjögren’s disease (SjD) is an autoimmune disease that primarily effects salivary and lacrimal glands. Currently, 4 million people in the US are affected with this disease, however, diagnosis is limited and there are no effective treatments to halt the autoimmune process. To study this disease, we utilize nonobese diabetic (NOD) mice, which spontaneously develop glandular inflammation similar to (SjD) patients. Our lab has shown that both CD4 and CD8 effector T cells play pathogenic roles to promote glandular inflammation. Additionally, we have found that IL-27 is required for disease development.

IL-27 is a heterodimeric cytokine that comprises EBI3 and p28 and binds IL-27 receptor which is also heterodimeric composed of gp130 and IL-27Rα. IL-27 has both immunostimulatory and immunoregulatory roles and has been shown to be involved in cancer, infections, and autoimmune diseases. IL-27 is elevated in the serum and saliva of Sjögren’s patients. Our lab has shown that both IL27p28 KO and IL27Rα KO NOD mice are protected from developing lacrimal gland disease. However, the mechanism by which IL-27 contributes to Sjögren’s is not fully elucidated.

The long-term goal of my research is to elucidate the early mechanisms of lacrimal gland autoimmunity and to understand the role of IL-27 in SjD-like autoimmunity.
 

Publications

Debreceni IL, Barr JY, Upton EM, Chen YG, Lieberman SM.
IL-27 promotes pathogenic T cells in a mouse model of Sjögren's disease. 
Clin Immunol. 2024 May 22;264:110260. doi: 10.1016/j.clim.2024.110260. Online ahead of print. PMID: 38788885

Debreceni IL, Barr JB, Upton EM, Chen Y, Lieberman SM. IL-27 promotes pathogenic T cells in a mouse model of Sjögren's disease. Clinical Immunology. 2024 May 22; 264:110260. doi: https://doi.org/10.1016/j.clim.2024.110260

Emmons TR, Giridharan T, Singel KL, Khan ANH, Ricciuti J, Howard K, Silva-Del Toro SL, Debreceni IL, Aarts CEM, Brouwer MC, Suzuki S, Kuijpers TW, Jongerius I, Allen LH, Ferreira VP, Schubart A, Sellner H, Eder J, Holland SM, Ram S, Lederer JA, Eng KH, Moysich KB, Odunsi K, Yaffe MB, Zsiros E, Segal BH. Mechanisms Driving Neutrophil-Induced T-cell Immunoparalysis in Ovarian Cancer. Cancer Immunol Res. 2021 Jul;9(7):790-810. doi: 10.1158/2326-6066.CIR-20-0922. Epub 2021 May 14. PMID: 33990375; PMCID: PMC8287091.

Debreceni IL, Chimenti MS, Serreze DV, Geurts AM, Chen YG, Lieberman SM. Toll-Like Receptor 7 Is Required for Lacrimal Gland Autoimmunity and Type 1 Diabetes Development in Male Nonobese Diabetic Mice. Int J Mol Sci. 2020 Dec 13;21(24):9478. doi: 10.3390/ijms21249478. PMID: 33322152; PMCID: PMC7764018.