Live imaging epidermal cell metabolism during inflammation: a new immunometabolic role for epidermal keratinocytes?

Abstract

Until recently, immunity and metabolism have existed as two distinct fields of research. Primarily driven by research into obesity-associated inflammation it is now clear that immunity and metabolism functionally intersect at specific nodes. This new field of research called immunometabolism seeks to understand how immune cell function is influenced by adaptive changes in metabolic processes. The concept of metabolic reprogramming, as a mechanism to guide the immune response, has primarily focused on how an immune cell’s metabolic mode can directly influence its activity. Whether non-hematopoietic cells, that also help orchestrate inflammation, utilize a similar mechanism to drive their immune activity is poorly understood. Due to their strategic location at the interface between the host and the environment, epidermal keratinocytes are highly adaptive cells that must respond to external stimuli by communicating to immune cells in the skin to generate an appropriate response. As such, keratinocytes are an important non-hematopoietic component of the immune system that function to maintain homeostasis, in part, by controlling inflammation within the skin. By live imaging epidermal cell metabolism during inflammation we have recently identified a new mechanism through which adaptive cell-intrinsic changes in epidermal cell metabolism helps direct their contribution to the immune response. During inflammation, epidermal cells elevate mitochondrial uptake of fatty acids (FAs) that, following b-oxidation, helps fuel matrix metalloproteinase production and leukocyte recruitment. We believe this represents the first example of metabolic reprogramming operating within a non-immune cell type to help orchestrate inflammation. Our results suggest that targeting the metabolic-immunological interface, at the level of the epidermal cell, may represent a new therapeutic strategy to alleviate inflammation that is associated with chronic skin diseases.