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

Immunity | Aug 26, 2011

http://www.ncbi.nlm.nih.gov/pubmed/21820333

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 RIS Download

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

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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:

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