Foxp3+ regulatory T (Treg) cells are critical to restrain self-reactive and inflammatory immune cells. Besides preserving immune homeostasis, Treg cells also perform several non-canonical functions that are essential to regulate multiple physiological processes and maintain tissue homeostasis. These functions include tissue repair, neuronal pruning, maintenance of organismal metabolism and curtailing fetal-maternal conflict. Most of these non-canonical functions are executed by Treg cells that reside in non-lymphoid tissues such as the muscle, pancreas, lung, brain, adipose or decidua. It is becoming increasingly clear that tissue or inflammatory micro-environment shapes the transcriptional landscape of resident Treg cells and contributes to their functional fitness. Therefore, to understand functional diversity, it is important to understand the tissue location of Treg cells and the factors that drive global and tissue-specific gene expression programs.
Treg cells develop from CD4+ T cell precursors by upregulating the master transcription factor Foxp3. The induction of Foxp3 occurs in the thymus and in the periphery, which distinguishes Treg cells based on their origin as thymic or peripheral Treg cells respectively. To be able to populate diverse tissues and perform multiple functions, Treg cells undergo further changes in the periphery to become functionally potent ‘effector’ Treg cells. Transcriptome analysis of Treg cells at single-cell and population-level identified multiple pathways involved in this potentiation. These include cytokine signaling (anti-inflammatory cytokine IL-10. IL33R), growth factors (amphiregulin), transcription factors (PPAR?, RORgt). Furthermore, effector Treg cells upregulate several chemokine receptors (CCR4, CCR6, CXCR3), integrins (CD103) and other homing molecules (GPR15) that allow migration to non-lymphoid tissues such as the adipose, gut, and lung. Within tissues, these cells further receive unique signals that induce a specific set of genes necessary to sustain and function in tissues. T cell receptor and co-stimulatory signals (e.g., TNF receptor signals) are central for homing and the peripheral differentiation of Treg cells. The ablation of either of these pathways would completely block differentiation and tissue localization of effector Treg cells. Deletion of tissue-specific factors or pathways, on the other hand, would affect Treg cells and their function in that particular tissue.
Differentiation and homeostatic requirements of Treg cells in tissue and inflammatory sites, therefore, could be harnessed to augment or block the function of Treg cells in a context or tissue-specific manner.
In this Research Topic, we welcome the submission of review, mini-review, original research and perspective articles that address but are not limited to, the following topics:
1. Tissue-resident Treg cells
2. Tissue adaptation mechanisms
3. Effector Treg cells pathways and functions
4. Treg cell stability and plasticity during inflammation
5. Treg cell canonical and non-canonical functions
6. Immune suppression mechanisms of Treg cells
7. Tumor-associated Treg cells
Foxp3+ regulatory T (Treg) cells are critical to restrain self-reactive and inflammatory immune cells. Besides preserving immune homeostasis, Treg cells also perform several non-canonical functions that are essential to regulate multiple physiological processes and maintain tissue homeostasis. These functions include tissue repair, neuronal pruning, maintenance of organismal metabolism and curtailing fetal-maternal conflict. Most of these non-canonical functions are executed by Treg cells that reside in non-lymphoid tissues such as the muscle, pancreas, lung, brain, adipose or decidua. It is becoming increasingly clear that tissue or inflammatory micro-environment shapes the transcriptional landscape of resident Treg cells and contributes to their functional fitness. Therefore, to understand functional diversity, it is important to understand the tissue location of Treg cells and the factors that drive global and tissue-specific gene expression programs.
Treg cells develop from CD4+ T cell precursors by upregulating the master transcription factor Foxp3. The induction of Foxp3 occurs in the thymus and in the periphery, which distinguishes Treg cells based on their origin as thymic or peripheral Treg cells respectively. To be able to populate diverse tissues and perform multiple functions, Treg cells undergo further changes in the periphery to become functionally potent ‘effector’ Treg cells. Transcriptome analysis of Treg cells at single-cell and population-level identified multiple pathways involved in this potentiation. These include cytokine signaling (anti-inflammatory cytokine IL-10. IL33R), growth factors (amphiregulin), transcription factors (PPAR?, RORgt). Furthermore, effector Treg cells upregulate several chemokine receptors (CCR4, CCR6, CXCR3), integrins (CD103) and other homing molecules (GPR15) that allow migration to non-lymphoid tissues such as the adipose, gut, and lung. Within tissues, these cells further receive unique signals that induce a specific set of genes necessary to sustain and function in tissues. T cell receptor and co-stimulatory signals (e.g., TNF receptor signals) are central for homing and the peripheral differentiation of Treg cells. The ablation of either of these pathways would completely block differentiation and tissue localization of effector Treg cells. Deletion of tissue-specific factors or pathways, on the other hand, would affect Treg cells and their function in that particular tissue.
Differentiation and homeostatic requirements of Treg cells in tissue and inflammatory sites, therefore, could be harnessed to augment or block the function of Treg cells in a context or tissue-specific manner.
In this Research Topic, we welcome the submission of review, mini-review, original research and perspective articles that address but are not limited to, the following topics:
1. Tissue-resident Treg cells
2. Tissue adaptation mechanisms
3. Effector Treg cells pathways and functions
4. Treg cell stability and plasticity during inflammation
5. Treg cell canonical and non-canonical functions
6. Immune suppression mechanisms of Treg cells
7. Tumor-associated Treg cells