Neutrophil free fatty acid receptors

Abstract

The human immune system protects against threats that range from microorganisms to damaged cells. Neutrophils, which are the most numerous cells of the innate immune system, circulate in the bloodstream in abundance. In the case of infection or damage, neutrophils are rapidly mobilized from the blood to affected tissues to eliminate the threat. The rapid response of neutrophils is dependent upon the ability to recognize structures that are predetermined as harmful, which is mediated by pattern recognition receptors expressed on the cell surface. Neutrophils express multiple receptors that not only detect danger but also other signals that orchestrate their functional responses.

FFA2R and GPR84 are neutrophil-expressed receptors that are capable of detecting short- and medium-chain free fatty acids, respectively. Whereas short-chain fatty acids are essentially produced by bacteria in the gut, medium-chain fatty acids are mainly acquired through the diet. Although the underlying physiological reason for neutrophil recognition of free fatty acids remains elusive, emerging evidence suggests that free fatty acids and their receptors exert a distinct and substantial influence on the inflammatory response.

Based on four original papers, this thesis highlights the intracellular signaling, regulatory processes and functional responses mediated by the neutrophil free fatty acid receptors. This thesis presents an overview of the current state of the art and aims to place the neutrophil free fatty acid receptors in a relevant context. The focus is on the FFA2R, to showcase the importance of this receptor in the control of inflammation.