National Institute of Dental and Craniofacial Research 1R21DE034962-01A1

Aging, Sex Bias, and CD8 T Cell Exhaustion in Salivary Gland Inflammation

This NIH-funded project investigates the immune mechanisms behind the age and sex bias in Sjögren’s Disease, focusing on salivary gland inflammation and CD8 T cell exhaustion using mouse models to inform therapeutic strategies.

Description

Sjögren’s Disease (SjD) is a systemic autoimmune disorder most frequently targeting exocrine glands and causing oral and ocular dryness. SjD is characterized by serum antibodies to nuclear and cytoplasmic antigens and salivary gland inflammation (sialoadenitis), which is associated with an increased risk of lymphoma. For unknown reasons, SjD disproportionately affects females and is typically diagnosed in the 5th-6th decade of life. The long-term goal of this project is to understand the age- and sex-related immune mechanisms involved in the salivary gland pathology of SjD. The proposed studies will utilize male and female mice that spontaneously develop the salient characteristics of SjD and mimic the age- and sex-bias of the disease. While both males and females develop systemic autoimmunity, only the females progress to severe sialoadenitis. The study will investigate whether the aged male salivary gland microenvironment harbors immunosuppressive signals that inhibit inflammation and will examine the differentiation trajectory of CD8 T cells targeting salivary gland antigens. The findings aim to inform the development of therapeutic strategies to alleviate salivary gland pathology in SjD.

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