T cell homeostasis and immune responses during disease progression in a mouse model for Rheumatoid arthritis

• Main Author: Ong, Joel Kai Li
• Other Authors: Pavanish Kumar
• Format: Final Year Project
• Language: English
• Published: 2017
• Subjects: DRNTU::Science
• Online Access: http://hdl.handle.net/10356/70675
• Institution: Nanyang Technological University

There is an unmet need to classify the cellular heterogeneity of Rheumatoid Arthritis (RA) patients throughout the course of disease. The collagen induced arthritis (CIA) model advantageously allows us to examine the murine immunome during disease development in a controlled environment. Mass cytometry was employed to categorize the splenic immune profile of diseased mice in comparison to normal mice. As autophagy’s role in lymphocyte homeostasis is becoming increasingly relevant, cells were also screened for autophagic flux via related markers. Several marked lymphocytic subsets that include novel and pre-existing cell types were discovered to be dysregulated in CIA mice splenocytes. A contrastingly heterogenous population of IL-10 producing B regulatory cells (Bregs) was uncovered with one subgroup displaying autophagic inhibition and diminished cell numbers in CIA mice. Although T Helper 17 (Th17) cells are generally enriched in CIA mice, the subset we identified was reduced, indicating an alternate function or external interference. CD4+ T Effector Memory cells in diseased mice also demonstrated increased autophagic activity. Even without confirmatory experiments, the data presented still provides compelling insights into the immune heterogeneity of CIA and RA.