Publication Database

Dendritic cells migrating into the dorsal root ganglia might play a central role in peripheral sensitization observed in chronic pruritic diseases (2023)

Art

Vortrag

Autoren

Singto, T. (WE 14)

Filor, V. (WE 14)

Vidak, J. (WE 14)

Bäumer, W. (WE 14)

Kongress

15th International Congress of the European Association for Veterinary Pharmacology and Toxicology

Bruges, Belgium, 02. – 05.07.2023

Quelle

Journal of veterinary pharmacology and therapeutics

Bandzählung: 46

Heftzählung: S1

Seiten: 45 – 46

ISSN: 1365-2885

Sprache

Englisch

Verweise

URL (Volltext): https://onlinelibrary.wiley.com/doi/10.1111/jvp.13203

DOI: 10.1111/jvp.13203

Kontakt

Institut für Pharmakologie und Toxikologie

Koserstr. 20
14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Introduction:
Signs of peripheral sensitization are found in the setting of chronic allergic skin diseases like canine atopic dermatitis. However, the mechanism of peripheral sensitization is poorly understood. As a way to study peripheral sensitization the chronic allergic contact dermatitis (ACD) model induced by toluene diisocyanate (TDI) in mice was utilized. In first experiments a significant increase in pruritogen-responsive neurons was observed in the dorsal root ganglia (DRG) excised from ACD mice. This enhanced response was accompanied by an influx of dendritic cells (DCs) into DRG. It is still unclear how DCs and neurons interact. Therefore, this study aims to investigate the role of DC influx to DRG in a chronic ACD condition.

Material and Methods:
BALB/C mice were repetitively challenged with TDI. The signs of ACD, expression of itch-related genes and peripheral sensitization by determination of pruritogen-induced Ca2+ signaling in sensory neurons were investigated. The influx of DCs into DRG was detected by immunohistochemistry as well as flow cytometry. A co-culture system was used to study the interaction between bone marrow derived DCs and DRG derived neurons in terms of peripheral sensitization. Pruritogen-induced intracellular Ca2+ increase in DRG neurons was compared between DRG monoculture and in co-culture with DC. The activation and expression of itch-related receptors was investigated using Ca2+ imaging, quantitative PCR, and immunocytochemistry. In this setting direct (co-incubation) and indirect co-culture (using a Transwell insert as a separator) were tested in parallel to determine if direct contact between cells is necessary.

Results:
TDI-sensitized mice showed increased scratching behavior, epidermal and dermal thickness, ear swelling, and eosinophil influx into ear skin. It was found that TDI-sensitized mice had an upregulated IL-31 receptor in their DRG. Excised DRG neurons were more frequently activated by pruritogens in TDI-sensitized mice. Immunohistochemistry and flow cytometry results also showed increased DC numbers in DRG of TDI-sensitized mice. The number of pruritogen-responsive neurons increased in DCs directly co-cultured with DRG, indicating peripheral sensitization, but this difference was lost in the indirect co-culture setting.

Conclusions:
This study indicates that there is an influx of DCs into DRG during TDI induced ACD and that these cells might play a role in the peripheral sensitization and direct cell–cell contact is necessary for interaction. Further studies are needed to characterize the mediator(s) that lead to peripheral sensitization in DRG neurons by activated DCs.