title: TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis.
abstract: Intestinal epithelial cells (IECs) produce thymic stromal lymphopoietin (TSLP); however, the in vivo influence of TSLP-TSLP receptor (TSLPR) interactions on immunity and inflammation in the intestine remains unclear. We show that TSLP-TSLPR interactions are critical for immunity to the intestinal pathogen Trichuris. Monoclonal antibody-mediated neutralization of TSLP or deletion of the TSLPR in normally resistant mice resulted in defective expression of Th2 cytokines and persistent infection. Susceptibility was accompanied by elevated expression of interleukin (IL) 12/23p40, interferon (IFN) gamma, and IL-17A, and development of severe intestinal inflammation. Critically, neutralization of IFN-gamma in Trichuris-infected TSLPR(-/-) mice restored Th2 cytokine responses and resulted in worm expulsion, providing the first demonstration of TSLPR-independent pathways for Th2 cytokine production. Additionally, TSLPR(-/-) mice displayed elevated production of IL-12/23p40 and IFN-gamma, and developed heightened intestinal inflammation upon exposure to dextran sodium sulfate, demonstrating a previously unrecognized immunoregulatory role for TSLP in a mouse model of inflammatory bowel disease.
authors.affiliation: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Betsy C
authors.initials: BC
authors.lastname: Taylor
authors.forename: Colby
authors.initials: C
authors.lastname: Zaph
authors.forename: Amy E
authors.initials: AE
authors.lastname: Troy
authors.forename: Yurong
authors.initials: Y
authors.lastname: Du
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Guild
authors.forename: Michael R
authors.initials: MR
authors.lastname: Comeau
authors.forename: David
authors.initials: D
authors.lastname: Artis
mesh_terms: D000818:Animals; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004847:Epithelial Cells / Q000378:metabolism; D007109:Immunity / Q000276:immunology*; D007136:Immunoglobulins; D007249:Inflammation / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40; D007422:Intestines / Q000276:immunology / Q000469:parasitology* / Q000473:pathology*; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D009500:Neutralization Tests; D018121:Receptors, Cytokine / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014257:Trichuriasis / Q000276:immunology* / Q000469:parasitology; D014258:Trichuris / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D007136:Immunoglobulins; D018836:Inflammation Mediators; D053762:Interleukin-12 Subunit p40; D018121:Receptors, Cytokine; C410591:Tslpr protein, mouse; D018664:Interleukin-12; D016264:Dextran Sulfate; D000094632:Thymic Stromal Lymphopoietin