The role of autophagy in intestinal T cell homeostasis

Thesis

A polymorphism in the essential autophagy gene ATG16L1 is associated with susceptibility to inflammatory bowel disease. However, the role of autophagy in maintenance of intestinal immune homeostasis remains unclear. Using targeted deletion of Atg16l1 in T cells, we demonstrate critical requirement for autophagy in generation of appropriate adaptive immune cell responses within the mucosa. Selective deletion of Atg16l1 in T cells resulted in spontaneous intestinal inflammation, characterized by accumulation of Th2 cells and aberrant antibody responses towards dietary and microbiota antigens. Foxp3⁺ Treg cells were dependent on autophagy for their survival and function within the intestinal lamina propria, where they acted to limit Th2 cell accumulation. In addition, we demonstrate a novel role for autophagy in limiting Th2 cell survival in a cell-intrinsic manner. The distinct requirements for autophagy in the survival of different intestinal CD4⁺ T cell subsets reveals a novel role for autophagy in mucosal T cell homeostasis, with potential implications for understanding and treatment of chronic inflammatory disorders.

Authors: Kabat, A

• DOI: 10.5287/ora-j51byjnrd
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: T cells; IBD; Mucosal immunology; Autophagy
• Subjects: Autophagy; Immunology