Cytokine storm and autoimmunity. Sjögren’s syndrome (SS) is a systemic autoimmune disorder affecting multiple organ systems. The targeting of exocrine salivary and lacrimal glands by a dysregulated immune response often leads to reduced fluid secretion, translating into the classic dry mouth and dry eye symptoms of the disorder. Genetic susceptibility plays a critical role in SS development, and genome-wide association studies have established that SS is a multi-genic disorder. The presence of viral nucleic acids and retroviral Line-1 elements in salivary gland cells, and an elevated type I IFN responsive gene signature, suggest that innate immune activation might be involved in SS’s etiology.
Nevertheless, how a systemic or/and localized innate immune response transitions into an adaptive autoimmune response targeting the exocrine glands remains unclear. This issue becomes even more critical in the context of the ongoing COVID-19 pandemic. The systemic cytokine storm elicited by the SARS-Cov-2 infection and the discovery of salivary gland tropism of this virus raises a strong possibility that a significant proportion of the population might develop SS. Thus, identifying pathways and mechanisms responsible for transitioning innate immunity activation into salivary gland disease and SS is a critical need of time.
In this project, using a unique genetic animal model resource, we are investigating how cytokine storms generated by excessive activation of innate immunity will lead to the development of SS and other autoimmune disorders.