Microbiota-induced tissue signals regulate ILC3-mediated antigen presentation

Frank Michael Lehmann; Nicole von Burg; Robert Ivanek; Claudia Teufel; Edit Horvath; Annick Peter; Gleb Turchinovich; Daniel Staehli; Tobias Eichlisberger; Mercedes Gomez de Agüero; Mairene Coto-Llerena; Michaela Prchal-Murphy; Veronika Sexl; Mohamed Bentires-Alj; Christoph Mueller; Daniela Finke

doi:10.1038/s41467-020-15612-2

Microbiota-induced tissue signals regulate ILC3-mediated antigen presentation

Frank Michael Lehmann, Nicole von Burg, Robert Ivanek, Claudia Teufel, Edit Horvath, Annick Peter, Gleb Turchinovich, Daniel Staehli, Tobias Eichlisberger, Mercedes Gomez de Agüero, Mairene Coto-Llerena, Michaela Prchal-Murphy, Veronika Sexl, Mohamed Bentires-Alj, Christoph Mueller, Daniela Finke^*

^*Corresponding author for this work

Department of Health Technology

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

Although group 3 innate lymphoid cells (ILC3s) are efficient inducers of T cell responses in the spleen, they fail to induce CD4⁺ T cell proliferation in the gut. The signals regulating ILC3-T cell responses remain unknown. Here, we show that transcripts associated with MHC II antigen presentation are down-modulated in intestinal natural cytotoxicity receptor (NCR)⁻ ILC3s. Further data implicate microbiota-induced IL-23 as a crucial signal for reversible silencing of MHC II in ILC3s, thereby reducing the capacity of ILC3s to present antigen to T cells in the intestinal mucosa. Moreover, IL-23-mediated MHC II suppression is dependent on mTORC1 and STAT3 phosphorylation in NCR⁻ ILC3s. By contrast, splenic interferon-γ induces MHC II expression and CD4⁺ T cell stimulation by NCR⁻ ILC3s. Our results thus identify biological circuits for tissue-specific regulation of ILC3-dependent T cell responses. These pathways may have implications for inducing or silencing T cell responses in human diseases.

Original language	English
Article number	1794
Journal	Nature Communications
Volume	11
Issue number	1
Number of pages	15
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-020-15612-2
Publication status	Published - 2020

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Lehmann, F. M., von Burg, N., Ivanek, R., Teufel, C., Horvath, E., Peter, A., Turchinovich, G., Staehli, D., Eichlisberger, T., Gomez de Agüero, M., Coto-Llerena, M., Prchal-Murphy, M., Sexl, V., Bentires-Alj, M., Mueller, C., & Finke, D. (2020). Microbiota-induced tissue signals regulate ILC3-mediated antigen presentation. Nature Communications, 11(1), Article 1794. https://doi.org/10.1038/s41467-020-15612-2

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title = "Microbiota-induced tissue signals regulate ILC3-mediated antigen presentation",

abstract = "Although group 3 innate lymphoid cells (ILC3s) are efficient inducers of T cell responses in the spleen, they fail to induce CD4+ T cell proliferation in the gut. The signals regulating ILC3-T cell responses remain unknown. Here, we show that transcripts associated with MHC II antigen presentation are down-modulated in intestinal natural cytotoxicity receptor (NCR)− ILC3s. Further data implicate microbiota-induced IL-23 as a crucial signal for reversible silencing of MHC II in ILC3s, thereby reducing the capacity of ILC3s to present antigen to T cells in the intestinal mucosa. Moreover, IL-23-mediated MHC II suppression is dependent on mTORC1 and STAT3 phosphorylation in NCR− ILC3s. By contrast, splenic interferon-γ induces MHC II expression and CD4+ T cell stimulation by NCR− ILC3s. Our results thus identify biological circuits for tissue-specific regulation of ILC3-dependent T cell responses. These pathways may have implications for inducing or silencing T cell responses in human diseases.",

author = "Lehmann, {Frank Michael} and {von Burg}, Nicole and Robert Ivanek and Claudia Teufel and Edit Horvath and Annick Peter and Gleb Turchinovich and Daniel Staehli and Tobias Eichlisberger and {Gomez de Ag{\"u}ero}, Mercedes and Mairene Coto-Llerena and Michaela Prchal-Murphy and Veronika Sexl and Mohamed Bentires-Alj and Christoph Mueller and Daniela Finke",

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Lehmann, FM, von Burg, N, Ivanek, R, Teufel, C, Horvath, E, Peter, A, Turchinovich, G, Staehli, D, Eichlisberger, T, Gomez de Agüero, M, Coto-Llerena, M, Prchal-Murphy, M, Sexl, V, Bentires-Alj, M, Mueller, C & Finke, D 2020, 'Microbiota-induced tissue signals regulate ILC3-mediated antigen presentation', Nature Communications, vol. 11, no. 1, 1794. https://doi.org/10.1038/s41467-020-15612-2

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T1 - Microbiota-induced tissue signals regulate ILC3-mediated antigen presentation

AU - Lehmann, Frank Michael

AU - von Burg, Nicole

AU - Ivanek, Robert

AU - Teufel, Claudia

AU - Horvath, Edit

AU - Peter, Annick

AU - Turchinovich, Gleb

AU - Staehli, Daniel

AU - Eichlisberger, Tobias

AU - Gomez de Agüero, Mercedes

AU - Coto-Llerena, Mairene

AU - Prchal-Murphy, Michaela

AU - Sexl, Veronika

AU - Bentires-Alj, Mohamed

AU - Mueller, Christoph

AU - Finke, Daniela

PY - 2020

Y1 - 2020

N2 - Although group 3 innate lymphoid cells (ILC3s) are efficient inducers of T cell responses in the spleen, they fail to induce CD4+ T cell proliferation in the gut. The signals regulating ILC3-T cell responses remain unknown. Here, we show that transcripts associated with MHC II antigen presentation are down-modulated in intestinal natural cytotoxicity receptor (NCR)− ILC3s. Further data implicate microbiota-induced IL-23 as a crucial signal for reversible silencing of MHC II in ILC3s, thereby reducing the capacity of ILC3s to present antigen to T cells in the intestinal mucosa. Moreover, IL-23-mediated MHC II suppression is dependent on mTORC1 and STAT3 phosphorylation in NCR− ILC3s. By contrast, splenic interferon-γ induces MHC II expression and CD4+ T cell stimulation by NCR− ILC3s. Our results thus identify biological circuits for tissue-specific regulation of ILC3-dependent T cell responses. These pathways may have implications for inducing or silencing T cell responses in human diseases.

AB - Although group 3 innate lymphoid cells (ILC3s) are efficient inducers of T cell responses in the spleen, they fail to induce CD4+ T cell proliferation in the gut. The signals regulating ILC3-T cell responses remain unknown. Here, we show that transcripts associated with MHC II antigen presentation are down-modulated in intestinal natural cytotoxicity receptor (NCR)− ILC3s. Further data implicate microbiota-induced IL-23 as a crucial signal for reversible silencing of MHC II in ILC3s, thereby reducing the capacity of ILC3s to present antigen to T cells in the intestinal mucosa. Moreover, IL-23-mediated MHC II suppression is dependent on mTORC1 and STAT3 phosphorylation in NCR− ILC3s. By contrast, splenic interferon-γ induces MHC II expression and CD4+ T cell stimulation by NCR− ILC3s. Our results thus identify biological circuits for tissue-specific regulation of ILC3-dependent T cell responses. These pathways may have implications for inducing or silencing T cell responses in human diseases.

U2 - 10.1038/s41467-020-15612-2

DO - 10.1038/s41467-020-15612-2

M3 - Journal article

C2 - 32286285

AN - SCOPUS:85083410263

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1794

ER -

Microbiota-induced tissue signals regulate ILC3-mediated antigen presentation

Abstract

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