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Thymic stromal lymphopoetin-induced expression of the endogenous inhibitory enzyme SLPI mediates recovery from colonic inflammation.

Thymic stromal lymphopoetin (TSLP) influences numerous immune functions, including those in the colonic mucosa. Here we report that TSLP-deficient (Tslp(-/-)) mice did not exhibit increased inflammation during dextran sodium sulfate (DSS)-induced colitis but failed to recover from disease, resulting in death. Increased localized neutrophil elastase (NE) activity during overt inflammation was observed in Tslp(-/-) mice and was paralleled by reduced expression of an endogenous inhibitor, secretory leukocyte peptidase inhibitor (SLPI). Pharmacological inhibition of NE or treatment with rSLPI reduced DSS-induced mortality in Tslp(-/-) mice. Signaling through TSLPR on nonhematopoietic cells was sufficient for recovery from DSS-induced colitis. Expression of the receptor occurred on intestinal epithelial cells (IEC), with stimulation inducing SLPI expression. Therefore, TSLP is critical in mediating mucosal healing after insult and functions in a nonredundant capacity that is independent of restraining T helper 1 (Th1) and Th17 cell cytokine production.

Pubmed ID: 21820333


  • Reardon C
  • Lechmann M
  • Brüstle A
  • Gareau MG
  • Shuman N
  • Philpott D
  • Ziegler SF
  • Mak TW



Publication Data

August 26, 2011

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI068731
  • Agency: NIAMS NIH HHS, Id: AR056113
  • Agency: NIAID NIH HHS, Id: R01 AI068731
  • Agency: NIAID NIH HHS, Id: R01 AI068731-05
  • Agency: NIAMS NIH HHS, Id: R01 AR056113
  • Agency: NIAMS NIH HHS, Id: R01 AR056113-01A1
  • Agency: Canadian Institutes of Health Research, Id:

Mesh Terms

  • Animals
  • Cells, Cultured
  • Colitis
  • Colon
  • Dextran Sulfate
  • Down-Regulation
  • Enzyme Activation
  • Immunity, Mucosal
  • Immunoglobulins
  • Inflammation
  • Intestinal Mucosa
  • Leukocyte Elastase
  • Mice
  • Mice, Knockout
  • Receptors, Cytokine
  • Recombinant Proteins
  • Secretory Leukocyte Peptidase Inhibitor
  • Signal Transduction