HIV remains a major global health challenge. While antiretroviral therapy (ART) has dramatically improved survival and quality of life, people living with HIV continue to face elevated risks of noncommunicable diseases such as cardiovascular disease and cancer. Many of these long-term complications are linked to chronic intestinal dysfunction, also called enteropathy, marked by crypt hyperplasia, villous atrophy, and breakdown of the epithelial barrier.
ART suppresses viral replication but fails to correct CD8⁺ T cell dysfunction and restore intestinal CD4⁺ T cells, which are essential for maintaining epithelial homeostasis via cytokines such as interferons (IFNs). Together, these immune aberrations lead to chronic inflammation.
How chronic interferon signaling and other inflammatory cues reprogram epithelial fate and regeneration is poorly understood. This project aims to define how persistent IFNγ signaling alters epithelial fate and regeneration using integrated in vitro and in vivo approaches, like murine intestinal organoids, CD4⁺ T cell-deficient mouse models, and human biopsies. We will elucidate the mechanism of enteropathy, focusing on the crosstalk between inflammatory and regenerative pathways, including WNT/β-catenin and Hippo-YAP/TAZ. This work aims to advance the understanding of immune-epithelial interactions with relevance to other gastrointestinal diseases like inflammatory bowel disease and colitis.
