ILC3s control splenic cDC homeostasis via lymphotoxin signaling

Matthias Vanderkerken; Antonio P. Baptista; Marco De Giovanni; Satoshi Fukuyama; Robin Browaeys; Charlotte L. Scott; Paula S. Norris; Gerard Eberl; James P. Di Santo; Eric Vivier; Yvan Saeys; Hamida Hammad; Jason G. Cyster; Carl F. Ware; Alexei V. Tumanov; Carl De Trez; Bart N. Lambrecht

doi:10.1084/jem.20190835

ILC3s control splenic cDC homeostasis via lymphotoxin signaling

Matthias Vanderkerken, Antonio P. Baptista, Marco De Giovanni, Satoshi Fukuyama, Robin Browaeys, Charlotte L. Scott, Paula S. Norris, Gerard Eberl, James P. Di Santo, Eric Vivier, Yvan Saeys, Hamida Hammad, Jason G. Cyster, Carl F. Ware, Alexei V. Tumanov, Carl De Trez, Bart N. Lambrecht

Department of Microbiology, Immunology & Molecular Genetics

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

The spleen contains a myriad of conventional dendritic cell (cDC) subsets that protect against systemic pathogen dissemination by bridging antigen detection to the induction of adaptive immunity. How cDC subsets differentiate in the splenic environment is poorly understood. Here, we report that LTα1β2-expressing Rorgt+ ILC3s, together with B cells, control the splenic cDC niche size and the terminal differentiation of Sirpα+CD4+Esam+ cDC2s, independently of the microbiota and of bone marrow pre-cDC output. Whereas the size of the splenic cDC niche depended on lymphotoxin signaling only during a restricted time frame, the homeostasis of Sirpα+CD4+Esam+ cDC2s required continuous lymphotoxin input. This latter property made Sirpα+CD4+Esam+ cDC2s uniquely susceptible to pharmacological interventions with LTβR agonists and antagonists and to ILC reconstitution strategies. Together, our findings demonstrate that LTα1β2-expressing Rorgt+ ILC3s drive splenic cDC differentiation and highlight the critical role of ILC3s as perpetual regulators of lymphoid tissue homeostasis.

Original language	English (US)
Article number	e20190835
Journal	Journal of Experimental Medicine
Volume	218
Issue number	5
DOIs	https://doi.org/10.1084/jem.20190835
State	Published - May 3 2021

ASJC Scopus subject areas

Medicine(all)

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10.1084/jem.20190835

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Vanderkerken, M., Baptista, A. P., Giovanni, M. D., Fukuyama, S., Browaeys, R., Scott, C. L., Norris, P. S., Eberl, G., Di Santo, J. P., Vivier, E., Saeys, Y., Hammad, H., Cyster, J. G., Ware, C. F., Tumanov, A. V., Trez, C. D., & Lambrecht, B. N. (2021). ILC3s control splenic cDC homeostasis via lymphotoxin signaling. Journal of Experimental Medicine, 218(5), Article e20190835. https://doi.org/10.1084/jem.20190835

Vanderkerken, M, Baptista, AP, Giovanni, MD, Fukuyama, S, Browaeys, R, Scott, CL, Norris, PS, Eberl, G, Di Santo, JP, Vivier, E, Saeys, Y, Hammad, H, Cyster, JG, Ware, CF, Tumanov, AV, Trez, CD & Lambrecht, BN 2021, 'ILC3s control splenic cDC homeostasis via lymphotoxin signaling', Journal of Experimental Medicine, vol. 218, no. 5, e20190835. https://doi.org/10.1084/jem.20190835

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title = "ILC3s control splenic cDC homeostasis via lymphotoxin signaling",

abstract = "The spleen contains a myriad of conventional dendritic cell (cDC) subsets that protect against systemic pathogen dissemination by bridging antigen detection to the induction of adaptive immunity. How cDC subsets differentiate in the splenic environment is poorly understood. Here, we report that LTα1β2-expressing Rorgt+ ILC3s, together with B cells, control the splenic cDC niche size and the terminal differentiation of Sirpα+CD4+Esam+ cDC2s, independently of the microbiota and of bone marrow pre-cDC output. Whereas the size of the splenic cDC niche depended on lymphotoxin signaling only during a restricted time frame, the homeostasis of Sirpα+CD4+Esam+ cDC2s required continuous lymphotoxin input. This latter property made Sirpα+CD4+Esam+ cDC2s uniquely susceptible to pharmacological interventions with LTβR agonists and antagonists and to ILC reconstitution strategies. Together, our findings demonstrate that LTα1β2-expressing Rorgt+ ILC3s drive splenic cDC differentiation and highlight the critical role of ILC3s as perpetual regulators of lymphoid tissue homeostasis.",

author = "Matthias Vanderkerken and Baptista, {Antonio P.} and Giovanni, {Marco De} and Satoshi Fukuyama and Robin Browaeys and Scott, {Charlotte L.} and Norris, {Paula S.} and Gerard Eberl and {Di Santo}, {James P.} and Eric Vivier and Yvan Saeys and Hamida Hammad and Cyster, {Jason G.} and Ware, {Carl F.} and Tumanov, {Alexei V.} and Trez, {Carl De} and Lambrecht, {Bart N.}",

note = "Funding Information: supported by a Marie-Sklodowska Curie Action fellowship as part of Horizon 2020; C.L. Scott is supported by the Fonds Wetenschappelijk Onderzoek Vlaanderen and a European Research Council starting grant; Y. Saeys is supported by the Fonds Wetenschappelijk Onderzoek Vlaanderen and the Marylou Ingram Scholar program; H. Hammad is supported by a research initiative grant from Ghent University; A.V. Tumanov is supported by grants from the National Institutes of Health (AI135574) and the Max and Minnie Tomerlin Voelcker Fund; and B.N. Lambrecht is supported by a European Research Council advanced grant, a research initiative grant from Ghent University, and an Excellence of Science research grant. Publisher Copyright: {\textcopyright} 2021 Rockefeller University Press. All rights reserved.",

year = "2021",

month = may,

day = "3",

doi = "10.1084/jem.20190835",

language = "English (US)",

volume = "218",

journal = "Journal of Experimental Medicine",

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T1 - ILC3s control splenic cDC homeostasis via lymphotoxin signaling

AU - Vanderkerken, Matthias

AU - Baptista, Antonio P.

AU - Giovanni, Marco De

AU - Fukuyama, Satoshi

AU - Browaeys, Robin

AU - Scott, Charlotte L.

AU - Norris, Paula S.

AU - Eberl, Gerard

AU - Di Santo, James P.

AU - Vivier, Eric

AU - Saeys, Yvan

AU - Hammad, Hamida

AU - Cyster, Jason G.

AU - Ware, Carl F.

AU - Tumanov, Alexei V.

AU - Trez, Carl De

AU - Lambrecht, Bart N.

N1 - Funding Information: supported by a Marie-Sklodowska Curie Action fellowship as part of Horizon 2020; C.L. Scott is supported by the Fonds Wetenschappelijk Onderzoek Vlaanderen and a European Research Council starting grant; Y. Saeys is supported by the Fonds Wetenschappelijk Onderzoek Vlaanderen and the Marylou Ingram Scholar program; H. Hammad is supported by a research initiative grant from Ghent University; A.V. Tumanov is supported by grants from the National Institutes of Health (AI135574) and the Max and Minnie Tomerlin Voelcker Fund; and B.N. Lambrecht is supported by a European Research Council advanced grant, a research initiative grant from Ghent University, and an Excellence of Science research grant. Publisher Copyright: © 2021 Rockefeller University Press. All rights reserved.

PY - 2021/5/3

Y1 - 2021/5/3

N2 - The spleen contains a myriad of conventional dendritic cell (cDC) subsets that protect against systemic pathogen dissemination by bridging antigen detection to the induction of adaptive immunity. How cDC subsets differentiate in the splenic environment is poorly understood. Here, we report that LTα1β2-expressing Rorgt+ ILC3s, together with B cells, control the splenic cDC niche size and the terminal differentiation of Sirpα+CD4+Esam+ cDC2s, independently of the microbiota and of bone marrow pre-cDC output. Whereas the size of the splenic cDC niche depended on lymphotoxin signaling only during a restricted time frame, the homeostasis of Sirpα+CD4+Esam+ cDC2s required continuous lymphotoxin input. This latter property made Sirpα+CD4+Esam+ cDC2s uniquely susceptible to pharmacological interventions with LTβR agonists and antagonists and to ILC reconstitution strategies. Together, our findings demonstrate that LTα1β2-expressing Rorgt+ ILC3s drive splenic cDC differentiation and highlight the critical role of ILC3s as perpetual regulators of lymphoid tissue homeostasis.

AB - The spleen contains a myriad of conventional dendritic cell (cDC) subsets that protect against systemic pathogen dissemination by bridging antigen detection to the induction of adaptive immunity. How cDC subsets differentiate in the splenic environment is poorly understood. Here, we report that LTα1β2-expressing Rorgt+ ILC3s, together with B cells, control the splenic cDC niche size and the terminal differentiation of Sirpα+CD4+Esam+ cDC2s, independently of the microbiota and of bone marrow pre-cDC output. Whereas the size of the splenic cDC niche depended on lymphotoxin signaling only during a restricted time frame, the homeostasis of Sirpα+CD4+Esam+ cDC2s required continuous lymphotoxin input. This latter property made Sirpα+CD4+Esam+ cDC2s uniquely susceptible to pharmacological interventions with LTβR agonists and antagonists and to ILC reconstitution strategies. Together, our findings demonstrate that LTα1β2-expressing Rorgt+ ILC3s drive splenic cDC differentiation and highlight the critical role of ILC3s as perpetual regulators of lymphoid tissue homeostasis.

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U2 - 10.1084/jem.20190835

DO - 10.1084/jem.20190835

M3 - Article

C2 - 33724364

AN - SCOPUS:85103227337

SN - 0022-1007

VL - 218

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 5

M1 - e20190835

ER -

ILC3s control splenic cDC homeostasis via lymphotoxin signaling

Abstract

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