Different populations of CD11b+ dendritic cells drive Th2 responses in the small intestine and colon

Johannes U. Mayer, Mimoza Demiri, William Winston Agace, Andrew S. MacDonald, Marcus Svensson Frej, Simon W. Milling

    Research output: Contribution to journalJournal articleResearchpeer-review

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    Abstract

    T-helper 2 (Th2) cell responses defend against parasites. Although dendritic cells (DCs) are vital for the induction of T-cell responses, the DC subpopulations that induce Th2 cells in the intestine are unidentified. Here we show that intestinal Th2 responses against Trichuris muris worms and Schistosoma mansoni eggs do not develop in mice with IRF-4-deficient DCs (IRF-4f/f CD11c-cre). Adoptive transfer of conventional DCs, in particular CD11b-expressing DCs from the intestine, is sufficient to prime S. mansoni-specific Th2 responses. Surprisingly, transferred IRF-4-deficient DCs also effectively prime S. mansoni-specific Th2 responses. Egg antigens do not induce the expression of IRF-4-related genes. Instead, IRF-4f/f CD11c-cre mice have fewer CD11b+ migrating DCs and fewer DCs carrying parasite antigens to the lymph nodes. Furthermore, CD11b+ CD103+ DCs induce Th2 responses in the small intestine, whereas CD11b+ CD103- DCs perform this role in the colon, revealing a specific functional heterogeneity among intestinal DCs in inducing Th2 responses.
    Original languageEnglish
    Article number15820
    JournalNature Communications
    Volume8
    ISSN2041-1723
    DOIs
    Publication statusPublished - 2017

    Bibliographical note

    This article is licensed under a Creative Commons Attribution 4.0 International License.

    Keywords

    • Antigen-presenting cells
    • Antimicrobial responses
    • Lymphocyte differentiation
    • Mucosal immunology

    Cite this

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    title = "Different populations of CD11b+ dendritic cells drive Th2 responses in the small intestine and colon",
    abstract = "T-helper 2 (Th2) cell responses defend against parasites. Although dendritic cells (DCs) are vital for the induction of T-cell responses, the DC subpopulations that induce Th2 cells in the intestine are unidentified. Here we show that intestinal Th2 responses against Trichuris muris worms and Schistosoma mansoni eggs do not develop in mice with IRF-4-deficient DCs (IRF-4f/f CD11c-cre). Adoptive transfer of conventional DCs, in particular CD11b-expressing DCs from the intestine, is sufficient to prime S. mansoni-specific Th2 responses. Surprisingly, transferred IRF-4-deficient DCs also effectively prime S. mansoni-specific Th2 responses. Egg antigens do not induce the expression of IRF-4-related genes. Instead, IRF-4f/f CD11c-cre mice have fewer CD11b+ migrating DCs and fewer DCs carrying parasite antigens to the lymph nodes. Furthermore, CD11b+ CD103+ DCs induce Th2 responses in the small intestine, whereas CD11b+ CD103- DCs perform this role in the colon, revealing a specific functional heterogeneity among intestinal DCs in inducing Th2 responses.",
    keywords = "Antigen-presenting cells, Antimicrobial responses, Lymphocyte differentiation, Mucosal immunology",
    author = "Mayer, {Johannes U.} and Mimoza Demiri and Agace, {William Winston} and MacDonald, {Andrew S.} and {Svensson Frej}, Marcus and Milling, {Simon W.}",
    note = "This article is licensed under a Creative Commons Attribution 4.0 International License.",
    year = "2017",
    doi = "10.1038/ncomms15820",
    language = "English",
    volume = "8",
    journal = "Nature Communications",
    issn = "2041-1723",
    publisher = "Nature Publishing Group",

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    Different populations of CD11b+ dendritic cells drive Th2 responses in the small intestine and colon. / Mayer, Johannes U.; Demiri, Mimoza; Agace, William Winston; MacDonald, Andrew S.; Svensson Frej, Marcus; Milling, Simon W.

    In: Nature Communications, Vol. 8, 15820, 2017.

    Research output: Contribution to journalJournal articleResearchpeer-review

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    T1 - Different populations of CD11b+ dendritic cells drive Th2 responses in the small intestine and colon

    AU - Mayer, Johannes U.

    AU - Demiri, Mimoza

    AU - Agace, William Winston

    AU - MacDonald, Andrew S.

    AU - Svensson Frej, Marcus

    AU - Milling, Simon W.

    N1 - This article is licensed under a Creative Commons Attribution 4.0 International License.

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    Y1 - 2017

    N2 - T-helper 2 (Th2) cell responses defend against parasites. Although dendritic cells (DCs) are vital for the induction of T-cell responses, the DC subpopulations that induce Th2 cells in the intestine are unidentified. Here we show that intestinal Th2 responses against Trichuris muris worms and Schistosoma mansoni eggs do not develop in mice with IRF-4-deficient DCs (IRF-4f/f CD11c-cre). Adoptive transfer of conventional DCs, in particular CD11b-expressing DCs from the intestine, is sufficient to prime S. mansoni-specific Th2 responses. Surprisingly, transferred IRF-4-deficient DCs also effectively prime S. mansoni-specific Th2 responses. Egg antigens do not induce the expression of IRF-4-related genes. Instead, IRF-4f/f CD11c-cre mice have fewer CD11b+ migrating DCs and fewer DCs carrying parasite antigens to the lymph nodes. Furthermore, CD11b+ CD103+ DCs induce Th2 responses in the small intestine, whereas CD11b+ CD103- DCs perform this role in the colon, revealing a specific functional heterogeneity among intestinal DCs in inducing Th2 responses.

    AB - T-helper 2 (Th2) cell responses defend against parasites. Although dendritic cells (DCs) are vital for the induction of T-cell responses, the DC subpopulations that induce Th2 cells in the intestine are unidentified. Here we show that intestinal Th2 responses against Trichuris muris worms and Schistosoma mansoni eggs do not develop in mice with IRF-4-deficient DCs (IRF-4f/f CD11c-cre). Adoptive transfer of conventional DCs, in particular CD11b-expressing DCs from the intestine, is sufficient to prime S. mansoni-specific Th2 responses. Surprisingly, transferred IRF-4-deficient DCs also effectively prime S. mansoni-specific Th2 responses. Egg antigens do not induce the expression of IRF-4-related genes. Instead, IRF-4f/f CD11c-cre mice have fewer CD11b+ migrating DCs and fewer DCs carrying parasite antigens to the lymph nodes. Furthermore, CD11b+ CD103+ DCs induce Th2 responses in the small intestine, whereas CD11b+ CD103- DCs perform this role in the colon, revealing a specific functional heterogeneity among intestinal DCs in inducing Th2 responses.

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    KW - Antimicrobial responses

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