The Role of pH and Proton Sensor GPR65 in Inflammation

pH is a critical environmental factor influencing human physiology. This doctorate thesis explores how pH modulates inflammation through a proton-sensor GPR65. It identifies that a genetic variant impairing GPR65 signalling increases risks of atopic dermatitis and high blood pressure. It further reveals that acidic skin pH and signalling of a proton-sensor, GPR65, suppress the onset of atopic dermatitis, a cutaneous inflammatory disease and that acidic colonic pH and GPR65 signalling mediate the protection by dietary fibre against high blood pressure, where inflammatory responses play a causal role. It also demonstrates the immune mechanisms underlying these discoveries.