Toll-like receptor 2 is important for the T(H)1 response to cutaneous sensitization.
BACKGROUND
Atopic dermatitis and allergic contact dermatitis are skin disorders triggered by epicutaneous sensitization with protein antigens and contact sensitization with haptens, respectively. Skin is colonized with bacteria, which are a source of Toll-like receptor (TLR) 2 ligands.


OBJECTIVE
We sought to examine the role of TLR2 in murine models of atopic dermatitis and allergic contact dermatitis.


METHODS
TLR2(-/-) mice and wild-type littermates were epicutaneously sensitized with ovalbumin (OVA) or contact sensitized with oxazolone (OX). Skin histology was assessed by means of hematoxylin and eosin staining and immunohistochemistry. Ear swelling was measured with a micrometer. Cytokine mRNA expression was examined by means of quantitative RT-PCR. Antibody levels and splenocyte secretion of cytokines in response to OVA stimulation were measured by means of ELISA. Dendritic cells were examined for their ability to polarize T-cell receptor/OVA transgenic naive T cells to T(H)1 and T(H)2.


RESULTS
In response to OVA sensitization, TLR2(-/-) mice experienced skin infiltration with eosinophils and CD4(+) cells, as well as upregulation of T(H)2 cytokine mRNAs that was comparable with that seen in wild-type littermates. In contrast, epidermal thickening, IFN-gamma expression in the skin, IFN-gamma production by splenocytes, and IgG2a anti-OVA antibody levels were impaired in TLR2(-/-) mice. After OX ear challenge, contact sensitized TLR2(-/-) mice exhibited defective ear swelling with impaired cellular infiltration, decreased epidermal thickening and local IFN-gamma expression, and impaired OX-specific IgG2a responses. Dendritic cells from TLR2(-/-) mice induced significantly lower production of IFN-gamma but normal IL-4 and IL-13 production in naive T cells.


CONCLUSIONS
These results indicate that TLR2 promotes the IFN-gamma response to cutaneously introduced antigens.
Division of Immunology, Children's Hospital, and the Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Haoli
H
Jin
Lalit
L
Kumar
Clinton
C
Mathias
David
D
Zurakowski
Hans
H
Oettgen
Leonid
L
Gorelik
Raif
R
Geha
D000818:Animals; D003876:Dermatitis, Atopic / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010081:Oxazolone / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000502:physiology*
D007074:Immunoglobulin G; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D010081:Oxazolone; D007371:Interferon-gamma; D010047:Ovalbumin