Author: Shaurya Patni
Advisors: Kate Fitzgerald & Kevin Crowthers
Category: First Year – Mass Academy
Abstract: Autoimmune diseases, impacting 10% of the population, lead to self-attacking immune responses, causing inflammation. In third world countries cases are increasing exponentially. Crohn’s disease, characterized by gastrointestinal inflammation, results in nutrient malabsorption, diarrhea, ulcers, and pain, often treated with immunosuppressive drugs that heighten infection risks. The inflammation creates opportunities for activating the STING pathway. The STING pathway exacerbates the situation by releasing pro-inflammatory chemokines and cytokines in the digestive system, causing further damage. This research evaluates Dimethyl fumarate (DMF) and Methotrexate (MTX) for inhibiting the cGAS-STING pathway, aiming for treatments with fewer side effects. Utilizing bone marrow-derived macrophages (BMDM) stimulated by diABZI, the study employed ELISA and rt-qPCR to measure the impact on pro-inflammatory markers like CXCL10, IL-6, TNFa, and IFNb, which were chosen as they are all essential markers of Crohn’s. Results indicated DMF and MTX significantly reduce inflammation, with DMF notably inhibiting the STING pathway at a transcriptional level, while MTX showed protein-level inhibition. This suggests a promising direction for Crohn’s disease management, offering more specific and less harmful treatments. The findings underscore the necessity for improved therapeutic approaches in the escalating global incidence of autoimmune diseases, emphasizing DMF and MTX’s potential in providing targeted relief and minimizing existing treatments’ immunosuppressive drawbacks. The study’s insights mark significant strides in autoimmune research, advocating a nuanced treatment model and setting the stage for subsequent investigations into side effects, immunogenicity, and combined medication efficacy.
UN SDGs:
SDG 3 – Good Health and Well-Being
SDG 10 – Reduced Inequalities
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