Research Topic

Thymus-derived, peripherally-derived and in vitro-induced T regulatory cells

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T regulatory cells (Tregs) are currently recognized as key players in immune regulation of both physiological and pathophysiological conditions. They are essential for maintaining peripheral tolerance, but they also contribute to the immunopathology of different diseases including cancers, infections, ...

T regulatory cells (Tregs) are currently recognized as key players in immune regulation of both physiological and pathophysiological conditions. They are essential for maintaining peripheral tolerance, but they also contribute to the immunopathology of different diseases including cancers, infections, allograft rejection, allergy and autoimmune diseases. Recent investigations showed that Tregs are not homogenous but rather heterogeneous populations of cells composed of discrete subsets with different phenotypes and functions. There are two main subsets of Tregs comprising the peripheral population of FoxP3+ Tregs: natural (nTregs) which are thymus derived and induced or adaptive (iTregs) which are induced in the periphery. In addition, there are two subsets (Tr1 and Th3) of FoxP3- iTregs.

Several studies showed that peripheral and local Treg levels are increased in cancer patients, which correlates with poor prognosis; however the exact mechanisms contributed to Treg accumulation remains unclear. Exploring which of these mechanisms may have a role in a specific cancer setting is of particular interest as some of the processes involved could be amenable to therapeutic intervention to allow targeting of Tregs in more specific immunotherapeutic protocols. Investigating whether Treg expansion involves nTregs or iTregs or both would provide greater insights into potential mechanisms of Treg elevation and cancer evasion. Recent work showed that Helios, an Ikarios family transcription factor, is expressed by natural CD4+FoxP3+ Tregs, but not by induced Tregs. However, the suitability of Helios as a specific marker was contradicted by reports from other studies that suggested Helios expression can be induced in vitro, depending on the method of activation rather than the origin of FoxP3+ cells.
In conclusion, there is an immense need to identify a surface marker or combination of surface markers to define/separate the different Treg subsets, which should enable further understanding of their phenotype, specificities, functions and roles in different diseases.
In this research topic, we are particularly interested in reviewing the different natural and induced Treg subsets and understanding their phenotypes, specificities, functions and mechanisms of suppression in different pathological conditions. Specifically, potential topics may include, but are not limited to the following areas:
- Subsets of T regulatory cells.
- Phenotypic and functional differences between natural and induced Tregs.
- How induced Tregs are generated.
- Natural and induced Tregs in cancer.
- Tregs in pathological conditions including infection, allograft rejection, allergy and autoimmune diseases.
- Targeting natural and induced Tregs for therapeutic benefits.
- Biotherapeutic potentials of natural and induced Tregs in autoimmune diseases and transplantation.



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