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

被引：431

作者：

Schmidt, Marc ^{[1
,2
]}

Raghavan, Badrinarayanan ^{[1
,2
]}

Mueller, Verena ^{[1
,2
]}

Vogl, Thomas ^{[3
]}

Fejer, Gyoergy ^{[4
]}

Tchaptchet, Sandrine ^{[4
]}

Keck, Simone ^{[4
]}

Kalis, Christoph ^{[4
]}

Nielsen, Peter J. ^{[4
]}

Galanos, Chris ^{[4
]}

Roth, Johannes ^{[3
]}

Skerra, Arne ^{[5
,6
]}

Martin, Stefan F. ^{[7
]}

Freudenberg, Marina A. ^{[4
]}

Goebeler, Matthias ^{[1
,2
]}

机构：

[1] Heidelberg Univ, Univ Hosp Mannheim, Dept Dermatol, D-6800 Mannheim, Germany

[2] Univ Giessen, Dept Dermatol, Giessen, Germany

[3] Univ Munster, Inst Immunol, Munster, Germany

[4] Max Planck Inst Immunobiol, D-7800 Freiburg, Germany

[5] Tech Univ Munich, Munich Ctr Integrated Prot Sci, D-8050 Freising Weihenstephan, Germany

[6] Tech Univ Munich, Chair Biol Chem, D-8050 Freising Weihenstephan, Germany

[7] Univ Med Ctr Freiburg, Dept Dermatol, Allergy Res Grp, Freiburg, Germany

来源：

NATURE IMMUNOLOGY | 2010年 / 11卷 / 09期

关键词：

NF-KAPPA-B; PROINFLAMMATORY GENE-EXPRESSION; ADAPTIVE IMMUNE-RESPONSES; INNATE IMMUNITY; ACTIVATION; RECOGNITION; MICE; SUSCEPTIBILITY; SENSITIZATION; ELICITATION;

D O I：

10.1038/ni.1919

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Allergies to nickel (Ni2+) 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 Ni2+ triggered an inflammatory response by directly activating human Toll-like receptor 4 (TLR4). Ni2+-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 Ni2+ but not by the natural ligand lipopolysaccharide. Accordingly, transgenic expression of human TLR4 in TLR4-deficient mice allowed efficient sensitization to Ni2+ 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.

引用

页码：814 / U64

页数：7

共 36 条

[1] NF-κB plays a major role in the maturation of human dendritic cells induced by NiSO4 but not by DNCB [J].