{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:32:48Z","timestamp":1791405168559,"version":"4.3.3"},"reference-count":66,"publisher":"Rockefeller University Press","issue":"9","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,9,1]]},"abstract":"<jats:p>Allergic contact hypersensitivity (CHS) is a T cell\u2013mediated inflammatory skin disease. Interleukin (IL)-12 is considered to be important in the generation of the allergen-specific T cell response. Loss of IL-12 function in IL-12R\u03b22\u2013deficient mice, however, did not ameliorate the allergic immune response, suggesting alternate IL-12\u2013independent pathways in the induction of CHS. Because exposure to contact allergens always takes place in the presence of microbial skin flora, we investigated the potential role of Toll-like receptors (TLRs) in the induction of CHS. Using mice deficient in TLR4, the receptor for bacterial lipopolysaccharide (LPS), IL-12 receptor (R) \u03b22, or both, we show that the concomitant absence of TLR4 and IL-12R\u03b22, but not the absence of TLR4 or IL-12R\u03b22 alone, prevented DC-mediated sensitization, generation of effector T cells, and the subsequent CHS response to 2,4,6-trinitro-1-chlorobenzene (TNCB), oxazolone, and fluorescein isothiocyanate. Introduction of the TLR4 transgene into the TLR4\/IL-12R\u03b22 mutant restored the CHS inducibility, showing a requirement for TLR4 in IL-12\u2013independent CHS induction. Furthermore, the concomitant absence of TLR2 and TLR4 prevented the induction of CHS to TNCB in IL-12\u2013competent mice. Finally, CHS was inducible in germ-free wild-type and IL-12R\u03b22\u2013deficient mice, but not in germ-free TLR4\/IL-12R\u03b22 double deficient mice, suggesting that the necessary TLR activation may proceed via endogenous ligands.<\/jats:p>","DOI":"10.1084\/jem.20070509","type":"journal-article","created":{"date-parts":[[2008,8,26]],"date-time":"2008-08-26T00:54:44Z","timestamp":1219712084000},"page":"2151-2162","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":196,"title":["Toll-like receptor and IL-12 signaling control susceptibility to contact hypersensitivity"],"prefix":"10.1084","volume":"205","author":[{"given":"Stefan F.","family":"Martin","sequence":"first","affiliation":[{"name":"1Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, D-79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan C.","family":"Dudda","sequence":"additional","affiliation":[{"name":"1Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, D-79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Bachtanian","sequence":"additional","affiliation":[{"name":"1Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, D-79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Lembo","sequence":"additional","affiliation":[{"name":"2Max Planck Institute for Immunobiology, D-79108 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Liller","sequence":"additional","affiliation":[{"name":"1Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, D-79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Du\u0308rr","sequence":"additional","affiliation":[{"name":"1Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, D-79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus M.","family":"Heimesaat","sequence":"additional","affiliation":[{"name":"3Institute for Microbiology and Hygiene, Charite\u0301-Universita\u0308tsmedizin Berlin, Charite\u0301 Campus Mitte, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Bereswill","sequence":"additional","affiliation":[{"name":"3Institute for Microbiology and Hygiene, Charite\u0301-Universita\u0308tsmedizin Berlin, Charite\u0301 Campus Mitte, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyo\u0308rgy","family":"Fejer","sequence":"additional","affiliation":[{"name":"2Max Planck Institute for Immunobiology, D-79108 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralitsa","family":"Vassileva","sequence":"additional","affiliation":[{"name":"2Max Planck Institute for Immunobiology, D-79108 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thilo","family":"Jakob","sequence":"additional","affiliation":[{"name":"1Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, D-79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus","family":"Freudenberg","sequence":"additional","affiliation":[{"name":"4Institute of Pathology, University Medical Center Freiburg, D-79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian C.","family":"Termeer","sequence":"additional","affiliation":[{"name":"1Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, D-79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Johner","sequence":"additional","affiliation":[{"name":"2Max Planck Institute for Immunobiology, D-79108 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Galanos","sequence":"additional","affiliation":[{"name":"2Max Planck Institute for Immunobiology, D-79108 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina A.","family":"Freudenberg","sequence":"additional","affiliation":[{"name":"2Max Planck Institute for Immunobiology, D-79108 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2008,8,25]]},"reference":[{"key":"2023072916323350000_BIB1","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1159\/000078765","volume":"134","year":"2004","journal-title":"Int. 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