Thymic stromal lymphopoetin-induced expression of the endogenous inhibitory enzyme SLPI mediates recovery from colonic inflammation.
Immunity
; 35(2): 223-35, 2011 Aug 26.
Article
em En
| MEDLINE
| ID: mdl-21820333
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.
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Base de dados:
MEDLINE
Assunto principal:
Imunoglobulinas
/
Receptores de Citocinas
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Colite
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Elastase de Leucócito
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Inibidor Secretado de Peptidases Leucocitárias
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Mucosa Intestinal
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article