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Event: 1707

Key Event Title

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

Increase, IL-23 from matured dendritic cells

Short name

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Increase of IL-23

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Biological Context

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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

Cell term
dendritic cell

Organ term

Organ term
immune system

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

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AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
Skin disease by stimulation of TLR7/8	KeyEvent	Evgeniia Kazymova (send email)	Under development: Not open for comment. Do not cite	Under Development

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

Increased IL-23 synthesis from TNF-α and inducible nitric oxide synthase (iNOS)-producing DCs (Tip-DCs) is a result of maturation from monocyte-derived dendritic cells (mo-DC) to Tip-DC which is HLA-DR⁺CD40⁺CD86⁺DC-Lamp⁺ and CD83⁺ (Farkas and Kemény. 2011, Wilsmann-Theis et al. 2013).

Tip-DCs are abundant in inflamed tissue such as skin in patients of chronic inflammatory skin disease, and not present in the steady-state or normal skin tissue. These cells are derived from monocyte infiltrated during inflammation and contribute to innate immune response to pathogens including bacteria and parasites (Guilliams et al. 2014).

Increased production of cytokines including IL-12/IL-23p40 in Tip-DC stimulated with R848, an agonist of Toll-like receptor (TLR) 7/8 was reported (Hänsel et al. 2011). In addition, maturation-dependent cytokine production including IL-23 from 6 hours in-vitro matured Tip-DC were observed when stimulated with CD40L and TLR ligands, such as LPS, PGN, Pam3Cys and R848 (Hänsel et al. 2011).

IL-23 is a heterodimer, sharing a p40 subunit with IL-12 but having a distinct p19 subunit. IL-23 binds to IL-12Rβ1 but not IL-12Rβ2. The receptor for this cytokine is heterodimeric and uses a novel second subunit, IL-23R, which is a member of the hematopoietin receptor family (Lee et al. 2004).

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

Measurement of IL23 protein

IL-23 in cell-free supernatants collected after R848 stimulation to moDCs is detected by ELISA (Schwarz et al. 2013).

Measurement of IL23 RNA levels

Expression of IL-23 mRNA in R848-stimulated moDCs is measured by qRT-PCR (Schwarz et al. 2013).

Domain of Applicability

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

Tip-DCs are also observed in mice. Murine Tip-DCs are defined as splenic CD11c⁺, CD11b⁺, MHC-II⁺, CD40⁺, and CD86⁺ cells producing iNOS and TNF. CD11b expression is observed in murine Tip-DC, however it is lacking on human cells (Lowes et al. 2005).

References

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

Farkas, A. and Kemény, L. (2011). Interferon-α in the generation of monocyte-derived dendritic cells: recent advances and implications for dermatology. British journal of dermatology 165(2), 247-254.
Guilliams, M., Ginhoux, F., Jakubzick, C., Naik, S.H., Onai, N., Schraml, B.U., Segura, E., Tussiwand, R. and Yona, S. (2014). Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nature review immunology 14(8), 571-578.
Hänsel, A., Günther, C., Ingwersen, J., Starke, J., Schmitz, M., Bechmann, M., Meurer, M., Rieber, E.P. and Schäkel, K. (2011). Human slan (6-sulfoLacNAc) dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong TH17/TH1 T-cell responses. Journal of allergy and clinical immunology 127(3), 787-794.
Lee, E., Trepicchio, W.L., Oestreicher, J.L., Pittman, D., Wang, F., Chamian, F., Dhodapkar, M. and Krueger, J.G. (2004). Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. Journal of experimental medicine 199(1), 125-130.
Lowes, M.A., Chamian, F., Abello, M.V., Fuentes-Duculan, J., Lin, S.L., Nussbaum, R., Novitskaya, I., Carbonaro, H., Cardinale, I., Kikuchi, T., Gilleaudeau, P., Sullivan-Whalen, M., Wittkowski, K.M., Papp, K., Garovoy, M., Dummer, W., Steinman, R.M. and Krueger, J.G. (2005). Increase in TNF-alpha and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a). Proceedings of the national academy of sciences of the United States of America 102(52), 19057-19062.
Schwarz, H., Posselt, G., Wurm, P., Ulbing, M., Duschl, A. and Horejs-Hoeck, J. (2013). TLR8 and NOD signaling synergistically induce the production of IL-1β and IL-23 in monocyte-derived DCs and enhance the expression of the feedback inhibitor SOCS2. Immunobiology 218(4), 533-42.
Wilsmann-Theis, D., Koch, S., Mindnich, C., Bonness, S., Schnautz, D., von Bubnoff, D. and Bieber, D. (2013). Generation and functional analysis of human TNF-α/iNOS-producing dendritic cells (Tip-DC). Allergy 68(7), 890-898.