Thymic stromal lymphopoietin is required for gastrointestinal allergy but not oral tolerance

Gastroenterology. 2010 Oct;139(4):1301-9. doi: 10.1053/j.gastro.2010.06.055. Epub 2010 Jun 23.


Background & aims: 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.

MeSH terms

  • Anaphylaxis / etiology
  • Animals
  • Cytokines / biosynthesis
  • Cytokines / physiology*
  • Dendritic Cells / physiology
  • Diarrhea / etiology
  • Food Hypersensitivity / etiology*
  • Gastrointestinal Tract / immunology*
  • Immune Tolerance*
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / immunology
  • Th2 Cells / immunology
  • Thymic Stromal Lymphopoietin


  • Cytokines
  • Ovalbumin
  • Thymic Stromal Lymphopoietin
  • TSLP protein, mouse