title: Thymic stromal lymphopoietin is required for gastrointestinal allergy but not oral tolerance.
abstract: OBJECTIVE
  Thymic stromal lymphopoietin (TSLP) is a cytokine produced by epithelial cells that acts on dendritic cells, mast cells, T cells, and B cells. TSLP is involved in the pathogenesis of allergic inflammation in the lung and skin, but data indicate a regulatory role in the gastrointestinal tract. We tested the functional role of TSLP in mouse models of gastrointestinal allergy and tolerance.
  
  
  METHODS
  TSLP Receptor (TSLPR)(+/+) and TSLPR(-/-) mice were sensitized and challenged with ovalbumin; models of allergic diarrhea or systemic anaphylaxis were studied. To induce oral tolerance, mice were fed with low-dose ovalbumin before they were immunized with it. Tolerance was measured from inhibition of ear swelling in a delayed-type hypersensitivity reaction.
  
  
  RESULTS
  TSLPR(-/-) mice were protected from the onset of allergic diarrhea; they did not develop mastocytosis in the jejunum and had reduced ovalbumin-immunoglobulin E in their serum, compared with TSLPR(+/+) mice. TSLPR(-/-) mice also lost T helper cell (Th) 2-mediated inflammation in the jejunum. In contrast, sensitization and oral tolerance were not impaired in TSLPR(-/-) mice. Transfer of wild-type, Th2-primed cells to TSLPR(-/-) mice completely restored the development of allergic diarrhea. Antigen presentation assays showed that TSLPR on T cells, but not dendritic cells, was required to mediate the Th2 response.
  
  
  CONCLUSIONS
  TSLP is required for allergic inflammation but not primary sensitization or tolerance to food proteins in the gastrointestinal tract; it amplifies Th2 responses directly from CD4(+) T cells.
authors.affiliation: The Jaffe Food Allergy Institute, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Blázquez
authors.forename: Lloyd
authors.initials: L
authors.lastname: Mayer
authors.forename: M Cecilia
authors.initials: MC
authors.lastname: Berin
mesh_terms: D000707:Anaphylaxis / Q000209:etiology; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology; D003967:Diarrhea / Q000209:etiology; D005512:Food Hypersensitivity / Q000209:etiology*; D041981:Gastrointestinal Tract / Q000276:immunology*; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D010047:Ovalbumin; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse