title: Migratory CD103+ dendritic cells suppress helminth-driven type 2 immunity through constitutive expression of IL-12.
abstract: CD8α(+) and CD103(+) dendritic cells (DCs) play a central role in the development of type 1 immune responses. However, their role in type 2 immunity remains unclear. We examined this issue using Batf3(-/-) mice, in which both of these DC subsets are missing. We found that Th2 cell responses, and related events such as eosinophilia, alternative macrophage activation, and immunoglobulin class switching to IgG1, were enhanced in Batf3(-/-) mice responding to helminth parasites. This had beneficial or detrimental consequences depending on the context. For example, Batf3 deficiency converted a normally chronic intestinal infection with Heligmosomoides polygyrus into an infection that was rapidly controlled. However, liver fibrosis, an IL-13-mediated pathological consequence of wound healing in chronic schistosomiasis, was exacerbated in Batf3(-/-) mice infected with Schistosoma mansoni. Mechanistically, steady-state production of IL-12 by migratory CD103(+) DCs, independent of signals from commensals or TLR-initiated events, was necessary and sufficient to exert the suppressive effects on Th2 response development. These findings identify a previously unrecognized role for migratory CD103(+) DCs in antagonizing type 2 immune responses.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Bart
authors.initials: B
authors.lastname: Everts
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Roxane
authors.initials: R
authors.lastname: Tussiwand
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Leentje
authors.initials: L
authors.lastname: Dreesen
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Keke C
authors.initials: KC
authors.lastname: Fairfax
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Stanley Ching-Cheng
authors.initials: SC
authors.lastname: Huang
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Amber M
authors.initials: AM
authors.lastname: Smith
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Christina M
authors.initials: CM
authors.lastname: O'Neill
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Wing Y
authors.initials: WY
authors.lastname: Lam
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Edelson
authors.affiliation: Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, Agriculture Research Service, US Department of Agriculture, Beltsville, MD 20705.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Urban
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Pearce
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D060467:Disease Resistance / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D006373:Helminthiasis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006376:Helminths / Q000276:immunology*; D007109:Immunity / Q000235:genetics; D007114:Immunization; D056747:Immunomodulation; D039001:Integrin alpha Chains / Q000378:metabolism*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics*; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D050976:Basic-Leucine Zipper Transcription Factors; D039001:Integrin alpha Chains; D012097:Repressor Proteins; C533289:SNFT protein, mouse; D051193:Toll-Like Receptors; C091367:alpha E integrins; D018664:Interleukin-12