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Event: 2324

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Increased of Treg/Th17 cell ratio

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Dysregulation of Treg/Th17 cell ratio
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
AhR activation leading to cancer progression KeyEvent Léo SPORTES-MILOT (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

The ratio between Th17 and T regulatory (Treg) cells is essential for maintaining a balanced immune environment (Noack and Miossec, 2014; Fasching et al., 2017; Lee, 2018). Both cells are derived from CD4+ lymphocytes, a subset of T lymphocytes.

On one hand, the role of Treg is to dampen the immune response by tempering the activity of CTLs, also called CD8+ cytotoxic T cells. Tregs are induced by TGF-β and FoxP3 (Forkhead box P3), which plays a major role in the activation from the naïve state to the activated Treg state. Consequently, the expression of FoxP3 well reflects the Treg activity (Fontenot et al., 2003); they are also characterized by a high expression of CD25 (Interleukin 2 receptor ɑ-chain). To highlight their immunosuppressive role in the TME, their elimination has been shown to lead to tumor immunity (Shimizu et al., 1999).

On the other hand, the role of Th17 cells is to enhance the immune response by producing pro-inflammatory signals like IL-17, IL-22, or IL-23. Naive T cells are also activated partly by TGF-β, but a co-stimulation with IL-6 or IL-21 is necessary; indeed, the absence of these proinflammatory cytokines leads to Treg differentiation instead (Bettelli et al., 2006).

In short, both Th17 and Treg require TGF-β to be activated; however, in a stressed environment, the production of IL-6 by other immune cells leads to a preferential differentiation towards the Th17 phenotype.

In cancer or in autoimmune diseases, this balance between the two phenotypes is disturbed  with a higher presence of Treg and leads to adverse outcomes such as tumor maintenance (Lin et al., 2019; He et al., 2020; Yan et al., 2020).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

References

List of the literature that was cited for this KE description. More help

Bettelli, E., Carrier, Y., Gao, W. et al. (2006). Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441, 235–238. https://doi.org/10.1038/nature04753.

Fasching, P., Stradner, M., Graninger, W. et al. (2017). Therapeutic Potential of Targeting the Th17/Treg Axis in Autoimmune Disorders. Molecules 22, 134. https://doi.org/10.3390/molecules22010134.

Fontenot, J. D., Gavin, M. A. and Rudensky, A. Y. (2003). Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 4, 330–336. https://doi.org/10.1038/ni904.

He, X., Liang, B. and Gu, N. (2020). Th17/Treg Imbalance and Atherosclerosis. Dis Markers 2020, 8821029. https://doi.org/10.1155/2020/8821029.

Lee, G. R. (2018). The Balance of Th17 versus Treg Cells in Autoimmunity. Int J Mol Sci 19, 730. https://doi.org/10.3390/ijms19030730.

Lin, W., Niu, Z., Zhang, H. et al. (2019). Imbalance of Th1/Th2 and Th17/Treg during the development of uterine cervical cancer. Int J Clin Exp Pathol 12, 3604–3612

Noack, M. and Miossec, P. (2014). Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun Rev 13, 668–677. https://doi.org/10.1016/j.autrev.2013.12.004.

Shimizu, J., Yamazaki, S. and Sakaguchi, S. (1999). Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J Immunol 163, 5211–5218

Yan, J.-B., Luo, M.-M., Chen, Z.-Y. et al. (2020). The Function and Role of the Th17/Treg Cell Balance in Inflammatory Bowel Disease. J Immunol Res 2020, 8813558. https://doi.org/10.1155/2020/8813558.