Mechanisms of inflammation-triggered taste loss and its recovery

Monell Chemical Senses Center, Philadelphia PA

Investigators

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Abstract

The sense of taste has evolved to detect nutrients and toxic substances in food and beverages. Taste dysfunction substantially affects health: severe taste loss leads to malnutrition, weight loss, and depression. Taste disorders can develop with various diseases, including many with underlying inflammation, such as infections, autoimmune diseases, and chronic inflammatory diseases. However, the mechanisms of taste disorders associated with these diseases are only poorly understood. Our recent research indicates that inflammation, characterized by induction of inflammatory cytokines and infiltration and activation of immune cells, contributes significantly to taste dysfunction. Yet, many aspects of how inflammation leads to taste disorders remain unknown. Furthermore, some patients suffer from long-term loss of taste following viral infections or other illnesses. The reason for the delayed recovery (or non-recovery) of taste in these patients is unclear; and there is no effective treatment for taste loss. The goal of this research is to elucidate the mechanisms of inflammation-associated taste loss and post-inflammation taste recovery. The inflammatory cytokine interferon-? (IFN-?) is highly induced in taste tissues from several disease models that have elevated inflammation and show taste abnormalities. IFNs when taken as medication for viral infection or cancer are associated with taste abnormalities. Yet, whether IFN-? directly contributes to taste disorders has not been determined. To test the role of IFN-? in taste dysfunction, we have established transgenic mouse strains that allow selective induction of IFN-? in particular cell types in taste tissues: taste progenitor/stem cells, sweet and umami receptor cells, and sour receptor cells. Here, we propose to use these mouse models to determine if and how IFN-? induction leads to taste dysfunction. We will investigate the effects of IFN-? on taste bud cell renewal, cell death, taste bud protective barriers, and immune cell trafficking in taste papillae. In addition, we will use one of the mouse strains that show severe taste loss after IFN-? induction to investigate how taste buds regenerate subsequent to inflammation. We will identify molecular and cellular processes that are critical for taste bud regeneration and functional recovery of taste. This research will lead to much-needed understanding of taste disorders and taste bud recovery and provide critical information for future development of therapeutic interventions.