Two sides of the same coin: intrinsic IL-27 signaling drives both TFH cells and exhausted CD4 T cells in a mouse model of Sjögren’s disease 4314

Abstract Description Sjögren’s disease (SjD) is an autoimmune disease that targets the exocrine glands. People with SjD experience profound dryness, joint pain, fatigue, and have an increased risk of developing lymphoma. There are currently no FDA approved therapies to treat the underlying immune dysfunction. Nonobese diabetic (NOD) mice provide a relevant model to study SjD, as they spontaneously develop T cell mediated inflammation of their lacrimal glands, similar to humans. IL-27 is upregulated in the salvia of children with SjD and is required for disease in NOD mice. IL-27 is a pleiotropic cytokine that has roles in driving both inflammatory and anti-inflammatory responses. Previously, we have shown that IL-27Rα signaling is required for CD4 T cells to transfer disease and that intrinsic IL-27 signaling drives two PD-1hi CD4 T cell populations in the lacrimal glands. Here, utilizing an adoptive co-transfer system and 27 color spectral flow cytometry, I further defined these PD-1hi populations to show that intrinsic IL-27 signaling drives TFH and CD39hiTCF-1loPD-1hi CD4 T cells. Further, when investigating the functionality of these cells, a higher frequency of TFH cells were CD107a+ and had higher levels of granzyme B, while CD39hi CD4 T cells produced less cytokines compared to other CD4 T cells, suggesting these CD39hi cells are exhausted CD4 T cells in the lacrimal glands. Taken together, these data demonstrate a dual role of IL-27 in promoting pathogenic CD4 T cells in SjD. Funding Sources Supported by NIH/NEI F31EY035130, NIH T32AI007485 to ILD, and NIH/NEI R01EY027731 to SML Topic Categories Basic Autoimmunity (BA)