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The severity of disease varies greatly in humans and mice; however, the genetic basis of such a heterogenous immune response remains poorly understood.\u00a0\u00a0 Here we show that, despite their close genetic relationship, C57BL\/10SnJ (B10) mice developed significantly more pronounced immunopathology and higher T helper 17 cell responses than C57BL\/6J (B6) mice. Similarly, live egg\u2010stimulated B10\u2010derived dendritic cells (DCs) produced significantly more IL\u20101\u03b2 and IL\u201023, resulting in higher IL\u201017 production by CD4 T cells.\u00a0 Gene expression analysis disclosed a heightened proinflammatory cytokine profile together with a strikingly lower expression of Ym1 in B10 versus B6 mice, consistent with failure of B10 DCs to attain alternative activation. To genetically dissect\u00a0the differential response, we developed and analyzed congenic mouse strains that capture major regions of allelic variation, and found that the level of inflammation was controlled\u00a0by\u00a0a relatively small number of\u00a0genes in a locus mapping to chromosome 4 117\u2013143 MB. Our study has thus identified novel genomic regions that regulate the severity of the schistosome infection by way of controlling the mode of DC activation and consequent CD4 T\u2010cell subset development.<\/jats:p>","DOI":"10.1002\/eji.201545547","type":"journal-article","created":{"date-parts":[[2015,5,9]],"date-time":"2015-05-09T10:04:50Z","timestamp":1431165890000},"page":"2312-2323","source":"Crossref","is-referenced-by-count":5,"title":["Minor genomic differences between related B6 and B10 mice affect severity of schistosome infection by governing the mode of dendritic cell activation"],"prefix":"10.1002","volume":"45","author":[{"given":"Patrick M.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Integrative Physiology and Pathobiology, Sackler School of Biomedical Sciences Tufts University School of Medicine  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Sproule","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor ME USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivek M.","family":"Philip","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor ME USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derry C.","family":"Roopenian","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor ME USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel J.","family":"Stadecker","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology and Pathobiology, Sackler School of Biomedical Sciences Tufts University School of Medicine  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,6,9]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"World Health Organization.Schistosomiasis Fact Sheet. 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