Environmental Exposures-The Missing Link in Immune Responses After Transplantation

In transplantation, immunosuppression has been directed at controlling acute responses, but treatment of chronic rejection has been ineffective. It is possible that factors that have previously been unaccounted for, such as exposure to inhaled pollution, ultraviolet light, or loss of the normal equilibrium between the gut immune system and the outside environment may be responsible for shifting immune responses to an effector/inflammatory phenotype, which leads to loss of self-tolerance and graft acceptance, and a shift towards autoimmunity and chronic rejection. Cells of the immune system are in a constant balance of effector response, regulation, and quiescence. Endogenous and exogenous signals can shift this balance through the aryl hydrocarbon receptor, which serves as a thermostat to modulate the response one way or the other, both at mucosal surfaces of interface organs to the outside environment, and in the internal milieu. Better understanding of this balance will identify a target for maintenance of self-tolerance and continued graft acceptance in patients who have achieved a "steady state" after transplantation.