Helminth products bypass the need for TSLP in Th2 immune responses by directly modulating dendritic cell function

Joanna C. Massacand, Rebecca C. Stettler, Reto Meier, Neil E. Humphreys, Richard K. Grencis, Benjamin J. Marsland, Nicola L. Harris

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine, mainly expressed by epithelial cells, and key to the development of allergic responses. The well-documented involvement of TSLP in allergy has led to the conviction that TSLP promotes the development of inflammatory Th2 cell responses. However, we now report that the interaction of TSLP with its receptor (TSLPR) has no functional impact on the development of protective Th2 immune responses after infection with 2 helminth pathogens, Heligmosomoides polygyrus and Nippostrongylus brasiliensis. Mice deficient in the TSLP binding chain of the TSLPR (TSLPR-/-) exhibited normal Th2 cell differentiation, protective immunity and memory responses against these two distinct rodent helminths. In contrast TSLP was found to be necessary for the development of protective Th2 responses upon infection with the helminth Trichuris muris (T. muris). TSLP inhibited IL-12p40 production in response to T. muris infection, and treatment of TSLPR-/- animals with neutralizing anti-IL-12p40 monoclonal antibody (mAb) was able to reverse susceptibility and attenuate IFN-γ production. We additionally demonstrated that excretory-secretory (ES) products from H. polygyrus and N. brasiliensis, but not T. muris, were capable of directly suppressing dendritic cell (DC) production of IL-12p40, thus bypassing the need for TSLP. Taken together, our data show that the primary function of TSLP is to directly suppress IL-12 secretion, thus supporting Th2 immune responses.

Original languageEnglish
Pages (from-to)13968-13973
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume106
Issue number33
DOIs
Publication statusPublished - 18 Aug 2009
Externally publishedYes

Cite this

Massacand, Joanna C. ; Stettler, Rebecca C. ; Meier, Reto ; Humphreys, Neil E. ; Grencis, Richard K. ; Marsland, Benjamin J. ; Harris, Nicola L. / Helminth products bypass the need for TSLP in Th2 immune responses by directly modulating dendritic cell function. In: Proceedings of the National Academy of Sciences. 2009 ; Vol. 106, No. 33. pp. 13968-13973.
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abstract = "Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine, mainly expressed by epithelial cells, and key to the development of allergic responses. The well-documented involvement of TSLP in allergy has led to the conviction that TSLP promotes the development of inflammatory Th2 cell responses. However, we now report that the interaction of TSLP with its receptor (TSLPR) has no functional impact on the development of protective Th2 immune responses after infection with 2 helminth pathogens, Heligmosomoides polygyrus and Nippostrongylus brasiliensis. Mice deficient in the TSLP binding chain of the TSLPR (TSLPR-/-) exhibited normal Th2 cell differentiation, protective immunity and memory responses against these two distinct rodent helminths. In contrast TSLP was found to be necessary for the development of protective Th2 responses upon infection with the helminth Trichuris muris (T. muris). TSLP inhibited IL-12p40 production in response to T. muris infection, and treatment of TSLPR-/- animals with neutralizing anti-IL-12p40 monoclonal antibody (mAb) was able to reverse susceptibility and attenuate IFN-γ production. We additionally demonstrated that excretory-secretory (ES) products from H. polygyrus and N. brasiliensis, but not T. muris, were capable of directly suppressing dendritic cell (DC) production of IL-12p40, thus bypassing the need for TSLP. Taken together, our data show that the primary function of TSLP is to directly suppress IL-12 secretion, thus supporting Th2 immune responses.",
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Helminth products bypass the need for TSLP in Th2 immune responses by directly modulating dendritic cell function. / Massacand, Joanna C.; Stettler, Rebecca C.; Meier, Reto; Humphreys, Neil E.; Grencis, Richard K.; Marsland, Benjamin J.; Harris, Nicola L.

In: Proceedings of the National Academy of Sciences, Vol. 106, No. 33, 18.08.2009, p. 13968-13973.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Massacand, Joanna C.

AU - Stettler, Rebecca C.

AU - Meier, Reto

AU - Humphreys, Neil E.

AU - Grencis, Richard K.

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AU - Harris, Nicola L.

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AB - Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine, mainly expressed by epithelial cells, and key to the development of allergic responses. The well-documented involvement of TSLP in allergy has led to the conviction that TSLP promotes the development of inflammatory Th2 cell responses. However, we now report that the interaction of TSLP with its receptor (TSLPR) has no functional impact on the development of protective Th2 immune responses after infection with 2 helminth pathogens, Heligmosomoides polygyrus and Nippostrongylus brasiliensis. Mice deficient in the TSLP binding chain of the TSLPR (TSLPR-/-) exhibited normal Th2 cell differentiation, protective immunity and memory responses against these two distinct rodent helminths. In contrast TSLP was found to be necessary for the development of protective Th2 responses upon infection with the helminth Trichuris muris (T. muris). TSLP inhibited IL-12p40 production in response to T. muris infection, and treatment of TSLPR-/- animals with neutralizing anti-IL-12p40 monoclonal antibody (mAb) was able to reverse susceptibility and attenuate IFN-γ production. We additionally demonstrated that excretory-secretory (ES) products from H. polygyrus and N. brasiliensis, but not T. muris, were capable of directly suppressing dendritic cell (DC) production of IL-12p40, thus bypassing the need for TSLP. Taken together, our data show that the primary function of TSLP is to directly suppress IL-12 secretion, thus supporting Th2 immune responses.

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