Metabolic Regulation of Allergic Inflammation

Queener, Ashley

doi:https://doi.org/10.21985/n2-yapc-f327

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Metabolic Regulation of Allergic Inflammation

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In the United States, allergic disease affects approximately 60 million people and impacts more people every year. While prevalence of allergic disease has steadily increased, there has concurrently been an increase in rates of metabolic syndrome—characterized by increased abdominal girth, decreased sensitivity to insulin, and higher levels of circulating blood glucose. These patients often experience chronic low-level inflammation, deemed meta-inflammation. Interestingly, patients with metabolic syndrome and related metabolic diseases also have increased rates of allergic disease and are over represented in the allergic population. Furthermore, patients with metabolic syndrome have increased severity of allergic inflammation, accounting for a disproportionate amount of healthcare spending and increased usage of sick time. While clinical work has been done to quantify these patient populations, there is a lack of understanding of the systemic metabolic processes that link allergic and metabolic diseases.This body of work examines the systemic connections between allergic lung inflammation and systemic metabolic tissues. We discover that 1) high glucose levels act as an adjuvant facilitate sensitization to OVA antigen, 2) mice sensitized under hyperglycemic conditions exhibit exacerbated lung inflammation, and 3) adipose tissue mounts a parallel Th2 inflammatory response during lung inflammation, characterized by infiltration of eosinophils and ILC2s and increased expression of Il4, Il5, Il13, and Il33. While Th2 immune cells are present in adipose tissue during homeostasis, this is the first report of increased Th2 activity in adipose tissue during inflammation. Furthermore, we discovered evidence of an antigen-specific effector response in adipose tissue, with adipose B cells producing OVA-specific IgE and adipose T cells proliferating in response to OVA restimulation. OVA-sensitized mice expressed a remodeling and development response in the adipose tissue and maintained glucose tolerance compared to saline mice. Taken together, our work suggests that the Th2 response in adipose tissue is mounted to maintain metabolic homeostasis during lung inflammatory events. Future complimentary studies should examine the necessity of healthy adipose tissue in resolving lung inflammation.

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