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

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• 作者：Colin Reardon¹ ;   ; ⁵ ; Matthias Lechmann¹ ;   ; ⁵ ;   ; ⁶ ; Anne Brü ; stle¹ ; Mé ; lanie  ; G. Gareau² ; Naomi Shuman¹ ; Dana Philpott³ ; Steven  ; F. Ziegler⁴ ; Tak  ; W. Mak¹ ;   ; ^{tmak@uhnres.utoronto.ca}
• 刊名：Immunity
• 出版年：2011
• 出版时间：26 August 2011
• 年：2011
• 卷：35
• 期：2
• 页码：223-235
• 全文大小：2137 K

文摘

Summary

Thymic stromal lymphopoetin (TSLP) influences numerous immune functions, including those in the colonic mucosa. Here we report that TSLP-deficient (Tslp^??/sup>) 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^??/sup> 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^??/sup> 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.