Immune Dysregulation in Inflammatory and Autoimmune Disorders

The immune system is an incredibly complex array of cells that performs the crucial function of host defense against a variety of foreign substances and pathogens. However, the system does not always function as intended, and dysregulation of the various mechanisms governing the immune response can lead to a variety of disease states. The complexity of immunological regulation makes clinical management of such disorders challenging. Doctors and patients must often balance ample immunological management with a variety of side-effects while combating resistance to treatment. The studies presented in this work aimed to elucidate various biological mechanisms governing immunological disorders, and to identify potential candidates for treatment targeting. We analyzed the similarities and differences between systemic lupus erythematosus and sarcoidosis, two immunological disorders that can affect virtually any organ system and have a wide array of presentations from mild and well controlled to rampant systemic inflammation and organ damage. We also analyzed the differences between mild and severe cases of COVID-19, a viral disease driven by hyperinflammation that similarly illustrates the destructive power of an unregulated immune response. We then studied the effects of COVID-19 vaccination in sarcoidosis to better understand the interaction of the sarcoidosis patient immune system with new mRNA vaccines. Lastly, we analyzed differences between mild and severe cases of sarcoidosis to characterize how severe disease differs and identify cellular contributors to severe disease. This work finds various imbalances in the regulation of inflammatory processes that drive the diseases studied, enabling further study of targeted treatments.