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CBA\/J (CBA) mice develop severe hepatic granulomatous inflammation associated with prominent Th17 cell responses driven by dendritic cell (DC)-derived IL-1\u03b2 and IL-23. Such Th17 cells fail to develop in low-pathology C57BL\/6 (BL\/6) mice, and the reasons for these strain-specific differences in APC reactivity to eggs remain unclear. We show by gene profiling that CBA DCs display an 18-fold higher expression of the C-type lectin receptor CD209a, a murine homolog of human DC-specific ICAM-3\u2013grabbing nonintegrin, compared with BL\/6 DCs. Higher CD209a expression was observed in CBA splenic and granuloma APC subpopulations, but only DCs induced Th17 cell differentiation in response to schistosome eggs. Gene silencing in CBA DCs and overexpression in BL\/6 DCs demonstrated that CD209a is essential for egg-elicited IL-1\u03b2 and IL-23 production and subsequent Th17 cell development, which is associated with SRC, RAF-1, and ERK1\/2 activation. These findings reveal a novel mechanism controlling the development of Th17 cell\u2013mediated severe immunopathology in helminthic disease.<\/jats:p>","DOI":"10.4049\/jimmunol.1400121","type":"journal-article","created":{"date-parts":[[2014,4,12]],"date-time":"2014-04-12T06:05:04Z","timestamp":1397282704000},"page":"4655-4665","source":"Crossref","is-referenced-by-count":42,"title":["CD209a Expression on Dendritic Cells Is Critical for the Development of Pathogenic Th17 Cell Responses in Murine Schistosomiasis"],"prefix":"10.1093","volume":"192","author":[{"given":"Holly E","family":"Ponichtera","sequence":"first","affiliation":[{"name":"Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine , Boston, MA 02111"},{"name":"Sackler School of Graduate Biomedical Sciences, Tufts University , Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara G","family":"Shainheit","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine , Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beiyun C","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine , Boston, MA 02111"},{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine , Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raktima","family":"Raychowdhury","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard , Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget M","family":"Larkin","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine , Boston, MA 02111"},{"name":"Sackler School of Graduate Biomedical Sciences, Tufts University , Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne M","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine , Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D Brenda","family":"Salantes","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine , Boston, MA 02111"},{"name":"Sackler School of Graduate Biomedical Sciences, Tufts University , Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Qiang","family":"Lai","sequence":"additional","affiliation":[{"name":"Nutritional Genomics Laboratory, Jean Mayer\u2013U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University , Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence D","family":"Parnell","sequence":"additional","affiliation":[{"name":"Nutritional Genomics Laboratory, Jean Mayer\u2013U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University , Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae J","family":"Yun","sequence":"additional","affiliation":[{"name":"Institut de Recherches Cliniques de Montr\u00e9al , Montr\u00e9al, Quebec H2W 1R7,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheolho","family":"Cheong","sequence":"additional","affiliation":[{"name":"Institut de Recherches Cliniques de Montr\u00e9al , Montr\u00e9al, Quebec H2W 1R7,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C","family":"Bunnell","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine , Boston, MA 02111"},{"name":"Sackler School of Graduate Biomedical Sciences, Tufts University , Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nir","family":"Hacohen","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard , Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel J","family":"Stadecker","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine , Boston, MA 02111"},{"name":"Sackler School of Graduate Biomedical Sciences, Tufts University , Boston, MA 02111"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,5,15]]},"reference":[{"key":"2025032404283838800_r1","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/S0891-5520(05)70122-7","article-title":"Hepatic schistosomiasis","volume":"14","author":"Bica","year":"2000","journal-title":"Infect. 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