RGD Reference Report - Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel. - Rat Genome Database

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Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel.

Authors: Schmidt, M  Raghavan, B  Muller, V  Vogl, T  Fejer, G  Tchaptchet, S  Keck, S  Kalis, C  Nielsen, PJ  Galanos, C  Roth, J  Skerra, A  Martin, SF  Freudenberg, MA  Goebeler, M 
Citation: Schmidt M, etal., Nat Immunol. 2010 Sep;11(9):814-9. doi: 10.1038/ni.1919. Epub 2010 Aug 15.
RGD ID: 7777133
Pubmed: PMID:20711192   (View Abstract at PubMed)
DOI: DOI:10.1038/ni.1919   (Journal Full-text)

Allergies to nickel (Ni(2+)) are the most frequent cause of contact hypersensitivity (CHS) in industrialized countries. The efficient development of CHS requires both a T lymphocyte-specific signal and a proinflammatory signal. Here we show that Ni(2+) triggered an inflammatory response by directly activating human Toll-like receptor 4 (TLR4). Ni(2+)-induced TLR4 activation was species-specific, as mouse TLR4 could not generate this response. Studies with mutant TLR4 proteins revealed that the non-conserved histidines 456 and 458 of human TLR4 are required for activation by Ni(2+) but not by the natural ligand lipopolysaccharide. Accordingly, transgenic expression of human TLR4 in TLR4-deficient mice allowed efficient sensitization to Ni(2+) and elicitation of CHS. Our data implicate site-specific human TLR4 inhibition as a potential strategy for therapeutic intervention in CHS that would not affect vital immune responses.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
allergic contact dermatitis  IDA 7777133 RGD 
allergic contact dermatitis  ISOTLR4 (Homo sapiens)7777133; 7777133 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tlr4  (toll-like receptor 4)

Genes (Mus musculus)
Tlr4  (toll-like receptor 4)

Genes (Homo sapiens)
TLR4  (toll like receptor 4)


Additional Information