Regulatory T cells (Tregs) are crucial for the establishment and maintenance of immunological homeostasis. They play a pivotal role in the regulation of immune responses toward self-antigens, commensal microorganisms, allergens, infectious agents, and tumors. Tregs modulate both innate and adaptive immune cells with a variety of suppressive mechanisms. Defects in Treg function have been associated with many autoimmune and allergic diseases, whereas complete loss of functional Tregs results in immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, a life-threatening autoimmune disorder.
Tregs might offer a great therapeutic potential to control unwanted immune responses. Without requiring systemic immune suppression, adoptive Treg transfer could provide long term tolerance in acute and chronic inflammatory diseases, transplantation medicine, as well as in atopy and allergies. Promising results in various animal disease models have led to investigations of the Treg therapy effects also in humans.
Besides many advantages, however, several issues regarding the possible translation of Treg immunotherapy into the clinical setting need to be addressed. Safety, potency, antigen specificity, functional stability, and long-term persistence represent critical points. In order to exploit the full potential and safety of adoptive Treg therapy, cells could be genetically modified before transfer. For instance, genetic modification of Treg antigen-specificity can increase their regulatory efficiency and considerably reduce required cell numbers. In addition, genetic engineering may improve cell targeting to the site of inflammation, provide regulation of functional properties (e.g. molecular on/off switches), and deliver key molecules needed for the immune control and tissue regeneration.
In this “Frontiers in Immunology” Research Topic, we would like to highlight the current status of in vitro and in vivo studies on using gene-modified Tregs in different pathological conditions and give an overview on possible future developments in cellular immunosuppressive therapies.
Regulatory T cells (Tregs) are crucial for the establishment and maintenance of immunological homeostasis. They play a pivotal role in the regulation of immune responses toward self-antigens, commensal microorganisms, allergens, infectious agents, and tumors. Tregs modulate both innate and adaptive immune cells with a variety of suppressive mechanisms. Defects in Treg function have been associated with many autoimmune and allergic diseases, whereas complete loss of functional Tregs results in immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, a life-threatening autoimmune disorder.
Tregs might offer a great therapeutic potential to control unwanted immune responses. Without requiring systemic immune suppression, adoptive Treg transfer could provide long term tolerance in acute and chronic inflammatory diseases, transplantation medicine, as well as in atopy and allergies. Promising results in various animal disease models have led to investigations of the Treg therapy effects also in humans.
Besides many advantages, however, several issues regarding the possible translation of Treg immunotherapy into the clinical setting need to be addressed. Safety, potency, antigen specificity, functional stability, and long-term persistence represent critical points. In order to exploit the full potential and safety of adoptive Treg therapy, cells could be genetically modified before transfer. For instance, genetic modification of Treg antigen-specificity can increase their regulatory efficiency and considerably reduce required cell numbers. In addition, genetic engineering may improve cell targeting to the site of inflammation, provide regulation of functional properties (e.g. molecular on/off switches), and deliver key molecules needed for the immune control and tissue regeneration.
In this “Frontiers in Immunology” Research Topic, we would like to highlight the current status of in vitro and in vivo studies on using gene-modified Tregs in different pathological conditions and give an overview on possible future developments in cellular immunosuppressive therapies.
