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TSLP‐TSLPR interactions license dendritic cell responses and CD4+ T cell dependent immunity and inflammation in the intestine
Author(s) -
Taylor Betsy C,
Zaph Colby,
Troy Amy E,
Du Yurong,
Guild Katherine,
Artis David
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.852.6
Subject(s) - proinflammatory cytokine , thymic stromal lymphopoietin , immunology , cytokine , immune system , inflammation , immunity , t cell , biology
Thymic stromal lymphopoeitin (TSLP) is an epithelial cell derived cytokine that has been shown to promote Th2 cytokine‐dependent inflammation in the skin and lung. However, the role of TSLP in regulating Th2 cytokine‐dependent immunity and inflammation in the intestine has not been tested. Utilizing TSLPR−/− mice we showed that TSLP‐TSLPR interactions are critical for immunity to the intestinal pathogen Trichuris. While littermate controls exhibited expression of Th2 cytokines and cleared infection, TSLPR−/− mice produced increased levels of Trichuris‐specific IFNγ and remained persistently infected. In vitro, pre‐exposure of DCs to rTSLP selectively inhibited LPS‐induced IL‐12/23p40 expression suggesting that TSLP functions to inhibit proinflammatory cytokines. To address whether TSLP‐TSLPR interactions were necessary for the induction of the protective Th2 cytokine response following Trichuris infection, TSLPR−/− mice were infected and treated with neutralizing anti‐IFNγ antibodies. Following anti‐IFNγ treatment, TSLPR−/− mice exhibited a protective Th2 immune response and cleared infection. Taken together, these data suggest that within the intestine TSLP‐TSLPR interactions are not required to directly promote pathogen‐specific Th2 cytokine responses, but instead create a Th2 permissive environment through inhibition of DC‐derived proinflammatory cytokines.