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Since IL-12 is important for the generation and maintenance of Th1 responses and may also inhibit Th2 cell generation from naive CD4 T cell precursors, it has been inferred that TLR4 signaling would have similar effects via the induction of IL-12 secretion. Surprisingly, we found that TLR4-defective mice subjected to sensitization and pulmonary challenge with a protein allergen had reductions in airway inflammation with eosinophils, allergen-specific IgE levels, and Th2 cytokine production, compared with wild-type mice. These reduced responses were attributable, at least in part, to decreased dendritic cell function: Dendritic cells from TLR4-defective mice expressed lower levels of CD86, a costimulatory molecule important for Th2 responses. They also induced less Th2 cytokine production by antigenically naive CD4 T cells in vitro and mediated diminished CD4 T cell Ag-specific pulmonary inflammation in vivo. These results indicate that TLR4 is required for optimal Th2 responses to Ags from nonpathogenic sources and suggest a role for TLR4 ligands, such as LPS derived from commensal bacteria or endogenously derived ligands, in maturation of the innate immune system before pathogen exposure.<\/jats:p>","DOI":"10.4049\/jimmunol.168.9.4524","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:46:54Z","timestamp":1398023214000},"page":"4524-4530","source":"Crossref","is-referenced-by-count":164,"title":["Toll-Like Receptor 4 Is Required for Optimal Development of Th2 Immune Responses: Role of Dendritic Cells"],"prefix":"10.1093","volume":"168","author":[{"given":"Karim","family":"Dabbagh","sequence":"first","affiliation":[{"name":"Department of Pediatrics and the Immunology Program, Stanford University School of Medicine , Stanford, CA 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin E","family":"Dahl","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and the Immunology Program, Stanford University School of Medicine , Stanford, CA 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Stepick-Biek","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and the Immunology Program, Stanford University School of Medicine , Stanford, CA 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and the Immunology Program, Stanford University School of Medicine , Stanford, CA 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2002,5,1]]},"reference":[{"key":"2026020209060155800_R1","first-page":"782","volume-title":"Nature","year":"2000"},{"key":"2026020209060155800_R2","first-page":"394","volume-title":"Nature","year":"1997"},{"key":"2026020209060155800_R3","first-page":"20","volume-title":"Curr. 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