Allergic contact dermatitis/irritant contact dermatitis toll-like receptor summary

Contact dermatitis classification	TLR member	Mechanism of action
Protein contact dermatitis	TLR4	TLR4 activation via Der-p2 MD-2 molecular mimicry of TLR4 accessory proteins.
ACD	TLR2	Activation via PAMP- and endogenous DAMP-induced pathway (eg, low molecular weight fragments of hyaluronic acid).
	TLR3	Activation during the elicitation phase due to exposure to allergens (eg, 2,4,5-trinitro-1-chlorobenzene, croton oil, etc).
	TLR4	Direct activation via nickel- or cobalt-induced dimerization of TLR4 histidine-rich ectodomains. Selective generation of antitumor T lymphocytes via Th1 and Th17 proliferation.
ICD	TLR3	Activation via PAMP- and DAMP-induced pathway. Activation due to keratinocyte damage induced by chronic irritant exposure.

ACD: allergic contact dermatitis; DAMP: damage-associated molecular pattern; ICD: irritant contact dermatitis; PAMP: pathogen-associated molecular pattern; Th: T helper; TLR: toll-like receptor.

Reproduced with permission from: Lee E, Kale A, Gaspari AA. Toll-like receptors and contact dermatitis. Dermatitis 2025; 36:14. Copyright © 2023 Mary Ann Liebert, Inc. The publisher for this copyrighted material is Mary Ann Liebert, Inc. publishers.

Graphic 147817 Version 1.0

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Allergic contact dermatitis/irritant contact dermatitis toll-like receptor summary