RGD Reference Report - TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis. - Rat Genome Database

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TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis.

Authors: Taylor, Betsy C  Zaph, Colby  Troy, Amy E  Du, Yurong  Guild, Katherine J  Comeau, Michael R  Artis, David 
Citation: Taylor BC, etal., J Exp Med. 2009 Mar 16;206(3):655-67. doi: 10.1084/jem.20081499. Epub 2009 Mar 9.
RGD ID: 38549593
Pubmed: PMID:19273626   (View Abstract at PubMed)
PMCID: PMC2699121   (View Article at PubMed Central)
DOI: DOI:10.1084/jem.20081499   (Journal Full-text)

Intestinal epithelial cells (IECs) produce thymic stromal lymphopoietin (TSLP); however, the in vivo influence of TSLP-TSLP receptor (TSLPR) interactions on immunity and inflammation in the intestine remains unclear. We show that TSLP-TSLPR interactions are critical for immunity to the intestinal pathogen Trichuris. Monoclonal antibody-mediated neutralization of TSLP or deletion of the TSLPR in normally resistant mice resulted in defective expression of Th2 cytokines and persistent infection. Susceptibility was accompanied by elevated expression of interleukin (IL) 12/23p40, interferon (IFN) gamma, and IL-17A, and development of severe intestinal inflammation. Critically, neutralization of IFN-gamma in Trichuris-infected TSLPR(-/-) mice restored Th2 cytokine responses and resulted in worm expulsion, providing the first demonstration of TSLPR-independent pathways for Th2 cytokine production. Additionally, TSLPR(-/-) mice displayed elevated production of IL-12/23p40 and IFN-gamma, and developed heightened intestinal inflammation upon exposure to dextran sodium sulfate, demonstrating a previously unrecognized immunoregulatory role for TSLP in a mouse model of inflammatory bowel disease.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TSLPHumantrichuriasis susceptibilityISOTslp (Mus musculus) RGD 
TslpRattrichuriasis susceptibilityISOTslp (Mus musculus) RGD 
TslpMousetrichuriasis susceptibilityIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tslp  (thymic stromal lymphopoietin)

Genes (Mus musculus)
Tslp  (thymic stromal lymphopoietin)

Genes (Homo sapiens)
TSLP  (thymic stromal lymphopoietin)


Additional Information