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Key Event Title
Increase, IL-23 from matured dendritic cells
|Level of Biological Organization|
Key Event Components
Key Event Overview
AOPs Including This Key Event
Key Event Description
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
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
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).
- 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.