Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation

Johanna Emgard; Hana Kammoun; Bethania Garcia-Cassani; Julie Chesne; Sara M Parigi; Jean-Marie Jacob; Hung-Wei Cheng; Elza Evren; Srustidhar Das; Paulo Czarnewski; Natalie Sleiers; Felipe Melo Gonzalez; Egle Kvedaraite; Mattias Svensson; Elke Scandella; Matthew Hepworth; Samuel Huber; Burkhard Ludewig; Lucie Peduto; Eduardo J Villablanca; Henrique Veiga-Fernandes; Joao P Pereira; Richard A Flavell; Tim Willinger

doi:10.1016/j.immuni.2017.11.020

Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation

Johanna Emgard, Hana Kammoun, Bethania Garcia-Cassani, Julie Chesne, Sara M Parigi, Jean-Marie Jacob, Hung-Wei Cheng, Elza Evren, Srustidhar Das, Paulo Czarnewski, Natalie Sleiers, Felipe Melo Gonzalez, Egle Kvedaraite, Mattias Svensson, Elke Scandella, Matthew Hepworth, Samuel Huber, Burkhard Ludewig, Lucie Peduto, Eduardo J VillablancaHenrique Veiga-Fernandes, Joao P Pereira, Richard A Flavell, Tim Willinger

Division of Immunology, Immunity to Infection and Respiratory Medicine

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

Abstract

Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation-induced increased oxysterol production caused colitis through GPR183-mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis.

Original language	English
Pages (from-to)	120-132
Number of pages	12
Journal	Immunity
Volume	48
Issue number	1
Early online date	16 Jan 2018
DOIs	https://doi.org/10.1016/j.immuni.2017.11.020
Publication status	Published - 16 Jan 2018

Keywords

Innate lymphoid cells
oxysterols
GPR183
EBI2
cell migration
Colon
lymphoid tissue
inflammation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Emgard, J., Kammoun, H., Garcia-Cassani, B., Chesne, J., Parigi, S. M., Jacob, J.-M., Cheng, H.-W., Evren, E., Das, S., Czarnewski, P., Sleiers, N., Melo Gonzalez, F., Kvedaraite, E., Svensson, M., Scandella, E., Hepworth, M., Huber, S., Ludewig, B., Peduto, L., ... Willinger, T. (2018). Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation. Immunity, 48(1), 120-132. https://doi.org/10.1016/j.immuni.2017.11.020

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title = "Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation",

abstract = "Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation-induced increased oxysterol production caused colitis through GPR183-mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis.",

keywords = "Innate lymphoid cells, oxysterols, GPR183, EBI2, cell migration, Colon, lymphoid tissue, inflammation",

author = "Johanna Emgard and Hana Kammoun and Bethania Garcia-Cassani and Julie Chesne and Parigi, {Sara M} and Jean-Marie Jacob and Hung-Wei Cheng and Elza Evren and Srustidhar Das and Paulo Czarnewski and Natalie Sleiers and {Melo Gonzalez}, Felipe and Egle Kvedaraite and Mattias Svensson and Elke Scandella and Matthew Hepworth and Samuel Huber and Burkhard Ludewig and Lucie Peduto and Villablanca, {Eduardo J} and Henrique Veiga-Fernandes and Pereira, {Joao P} and Flavell, {Richard A} and Tim Willinger",

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month = jan,

day = "16",

doi = "10.1016/j.immuni.2017.11.020",

language = "English",

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issn = "1074-7613",

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Emgard, J, Kammoun, H, Garcia-Cassani, B, Chesne, J, Parigi, SM, Jacob, J-M, Cheng, H-W, Evren, E, Das, S, Czarnewski, P, Sleiers, N, Melo Gonzalez, F, Kvedaraite, E, Svensson, M, Scandella, E, Hepworth, M, Huber, S, Ludewig, B, Peduto, L, Villablanca, EJ, Veiga-Fernandes, H, Pereira, JP, Flavell, RA & Willinger, T 2018, 'Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation', Immunity, vol. 48, no. 1, pp. 120-132. https://doi.org/10.1016/j.immuni.2017.11.020

TY - JOUR

T1 - Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation

AU - Emgard, Johanna

AU - Kammoun, Hana

AU - Garcia-Cassani, Bethania

AU - Chesne, Julie

AU - Parigi, Sara M

AU - Jacob, Jean-Marie

AU - Cheng, Hung-Wei

AU - Evren, Elza

AU - Das, Srustidhar

AU - Czarnewski, Paulo

AU - Sleiers, Natalie

AU - Melo Gonzalez, Felipe

AU - Kvedaraite, Egle

AU - Svensson, Mattias

AU - Scandella, Elke

AU - Hepworth, Matthew

AU - Huber, Samuel

AU - Ludewig, Burkhard

AU - Peduto, Lucie

AU - Villablanca, Eduardo J

AU - Veiga-Fernandes, Henrique

AU - Pereira, Joao P

AU - Flavell, Richard A

AU - Willinger, Tim

PY - 2018/1/16

Y1 - 2018/1/16

N2 - Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation-induced increased oxysterol production caused colitis through GPR183-mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis.

AB - Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation-induced increased oxysterol production caused colitis through GPR183-mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis.

KW - Innate lymphoid cells

KW - oxysterols

KW - GPR183

KW - EBI2

KW - cell migration

KW - Colon

KW - lymphoid tissue

KW - inflammation

U2 - 10.1016/j.immuni.2017.11.020

DO - 10.1016/j.immuni.2017.11.020

M3 - Article

SN - 1074-7613

VL - 48

SP - 120

EP - 132

JO - Immunity

JF - Immunity

IS - 1

ER -

Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation

Abstract

Keywords

UN SDGs

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