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The Journal of Allergy and Clinical Immunology
Volume 123, Issue 4
, Pages
875-882.e1
, April 2009
Toll-like receptor 2 is important for the TH1 response to cutaneous sensitization
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TLR2 mRNA expression after skin tape stripping and painting with OX. Quantitative PCR analysis of TLR2 mRNA expression in mouse skin after tape stripping (n = 5; A) or application of 2% OX in ethanol
TLR2 mRNA expression after skin tape stripping and painting with OX. Quantitative PCR analysis of TLR2 mRNA expression in mouse skin after tape stripping (n = 5; A) or application of 2% OX in ethanol to shaved skin (n = 4; B) is shown. Results were normalized for glyceraldehyde-3-phosphate dehydrogenase expression and expressed as fold induction compared with time 0. Values are presented as the mean ± SD. ∗P < .05.
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Impaired epidermal thickening and IFN-γ mRNA expression but normal cellular infiltration and TH2 cytokine production in OVA-sensitized skin of TLR2−/− mice. A, Representative skin histology (originalImpaired epidermal thickening and IFN-γ mRNA expression but normal cellular infiltration and TH2 cytokine production in OVA-sensitized skin of TLR2−/− mice. A, Representative skin histology (original magnification ×200). B, Skin-infiltrating CD4+ T cells and eosinophils. C, Quantitative PCR analysis of mRNA levels of IL-4, IL-15, and IL-13 and IFN-γ. n = 6-7. ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001. SAL, Saline; KO, knockout.
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Impaired TH1 systemic response to epicutaneous sensitization with OVA in TLR2−/− mice. A, Cytokine secretion by splenocytes in response to OVA stimulation in vitro. B, Serum levels of OVA-specific immImpaired TH1 systemic response to epicutaneous sensitization with OVA in TLR2−/− mice. A, Cytokine secretion by splenocytes in response to OVA stimulation in vitro. B, Serum levels of OVA-specific immunoglobulin isotypes. n = 6-7. ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001. SAL, Saline; KO, knockout.
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Impaired contact hypersensitivity in TLR2−/− mice. A, Ear swelling in sensitized mice challenged with OX hapten. Results represent the difference in thickness between hapten- and vehicle-challenged eaImpaired contact hypersensitivity in TLR2−/− mice. A, Ear swelling in sensitized mice challenged with OX hapten. Results represent the difference in thickness between hapten- and vehicle-challenged ears (n = 10). B, Representative ear skin histology at 24 hours after challenge (original magnification ×200). C and D, IL-4 (Fig 4, C) and IFN-γ (Fig 4, D) mRNA expression as fold induction in hapten-challenged over vehicle-challenged ears. ∗P < .05, ∗∗P < .01, and ∗∗∗P < .0001. KO, Knockout.
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Impaired OX-specific IgG2a response in TLR2−/− mice. Serum anti-OX IgG1 and IgG2a levels in mice sensitized and challenged with OX. Serum was taken 24 hours after the challenge. ∗P < .05, ∗∗P < .01, aImpaired OX-specific IgG2a response in TLR2−/− mice. Serum anti-OX IgG1 and IgG2a levels in mice sensitized and challenged with OX. Serum was taken 24 hours after the challenge. ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001. KO, Knockout.
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Impaired capacity of TLR2−/− DCs to drive a TH1 response. Proliferation (A) and secretion of IL-4 (B), IL-13 (C), and IFN-γ (D) by CD4+ OTII T cells stimulated with OVA323-339 peptide in the presenceImpaired capacity of TLR2−/− DCs to drive a TH1 response. Proliferation (A) and secretion of IL-4 (B), IL-13 (C), and IFN-γ (D) by CD4+ OTII T cells stimulated with OVA323-339 peptide in the presence of CD11c+ splenic DCs derived from WT and TLR2−/− mice. Data are representative of 3 experiments. ∗P < .05 and ∗∗P < .01. 3H-Td, Tritiated thymidine; KO, knockout.
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CCL17/thymus and activation-regulated (TARC) chemokine (A) and CCL11/eotaxin-1 (B) mRNA expression in OVA-sensitized skin of TLR2−/− mice (n = 5-6). ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001. SAL, saline;CCL17/thymus and activation-regulated (TARC) chemokine (A) and CCL11/eotaxin-1 (B) mRNA expression in OVA-sensitized skin of TLR2−/− mice (n = 5-6). ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001. SAL, saline; KO, knockout.
Supported by the Atopic Dermatitis and Vaccinia Immunization Network; National Institutes of Health/National Institute of Allergy and Infectious Diseases contract NO1 (AI 40030); and a US Public Health Service grant AR-047417 to R.G. H.J. has received a postdoctoral fellowship from the American Heart Association.
Disclosure of potential conflict of interest: H. Jin has received research support from the American Heart Association. H. Oettgen has served as a consultant and scientific advisor for Schering-Plough and as a consultant for Genentech and has received research support from Novartis. L. Gorelik is employed by Biogen Idec, Inc. The rest of the authors have declared that they have no conflict of interest.
PII: S0091-6749(09)00233-4
doi: 10.1016/j.jaci.2009.02.007
© 2009 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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The Journal of Allergy and Clinical Immunology
Volume 123, Issue 4
, Pages
875-882.e1
, April 2009
