Targeting in ammation to improve regulatory T cell therapy for immunopathologies

Overview & Synopsis

Inflammation is a normal, transient physiological defense against infectious diseases. However, in many chronic conditions such as autoimmune diseases (AIDs) or graft rejections, the inflammatory response lingers on, leading to significant damage. Long-term immunosuppressive treatments are usually prescribed in these diseases, with insufficient efficacy and significant side effects that impact patients’ quality of life. Foxp3 regulatory T cells (Tregs)—important in inducing and maintaining peripheral tolerance—are key to preventing excessive immune responses and efficiently suppress AIDs. Promising preclinical and clinical studies have suggested that stimulating one’s own Tregs, or adoptive cell therapy (ACT) using Tregs, may lead to new treatments for some AIDs and in cases of graft rejection (1). However, the challenge with these therapies is to obtain local and long-term suppression specifically in the target organ damaged by detrimental inflammation. With this in mind, Bittner et al. present in PNAS a cell therapy using Tregs expressing a transgenic receptor sensing inflammation (2). Here, I will review advantages and open questions of this innovative therapeutic approach for immunopathologies.