Toll-like receptor 2 is important for the TH1 response to cutaneous sensitization Haoli Jin, MD, PhD, Lalit Kumar, PhD, Clinton Mathias, PhD, David Zurakowski,

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Toll-like receptor 2 is important for the TH1 response to cutaneous sensitization Haoli Jin, MD, PhD, Lalit Kumar, PhD, Clinton Mathias, PhD, David Zurakowski, PhD, Hans Oettgen, MD, PhD, Leonid Gorelik, PhD, Raif Geha, MD Journal of Allergy and Clinical Immunology Volume 123, Issue 4, Pages 875-882.e1 (April 2009) DOI: 10.1016/j.jaci.2009.02.007 Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 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. Journal of Allergy and Clinical Immunology 2009 123, 875-882.e1DOI: (10.1016/j.jaci.2009.02.007) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 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 (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. Journal of Allergy and Clinical Immunology 2009 123, 875-882.e1DOI: (10.1016/j.jaci.2009.02.007) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 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 immunoglobulin isotypes. n = 6-7. ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001. SAL, Saline; KO, knockout. Journal of Allergy and Clinical Immunology 2009 123, 875-882.e1DOI: (10.1016/j.jaci.2009.02.007) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 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 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. Journal of Allergy and Clinical Immunology 2009 123, 875-882.e1DOI: (10.1016/j.jaci.2009.02.007) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 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, and ∗∗∗P < .001. KO, Knockout. Journal of Allergy and Clinical Immunology 2009 123, 875-882.e1DOI: (10.1016/j.jaci.2009.02.007) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 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 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. Journal of Allergy and Clinical Immunology 2009 123, 875-882.e1DOI: (10.1016/j.jaci.2009.02.007) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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. Journal of Allergy and Clinical Immunology 2009 123, 875-882.e1DOI: (10.1016/j.jaci.2009.02.007) Copyright © 2009 American Academy of Allergy, Asthma & Immunology Terms and Conditions