Thymic Stromal Lymphopoetin-Induced Expression of the Endogenous Inhibitory Enzyme SLPI Mediates Recovery from Colonic Inflammation

Colin Reardon, Matthias Lechmann, Anne Brüstle, Mélanie G. Gareau, Naomi Shuman, Dana Philpott, Steven F. Ziegler, Tak W. Mak*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

95 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)223-235
Number of pages13
JournalImmunity
Volume35
Issue number2
DOIs
Publication statusPublished - 26 Aug 2011
Externally publishedYes

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