Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A2BAR signaling in intestinal epithelial cells

Darine W. El-Naccache; Fei Chen; Mark J. Palma; Alexander Lemenze; Matthew A. Fischer; Wenhui Wu; Pankaj K. Mishra; Holger K. Eltzschig; Simon C. Robson; Francesco Di Virgilio; George S. Yap; Karen L. Edelblum; György Haskó; William C. Gause

doi:10.1016/j.celrep.2022.111150

Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A_2BAR signaling in intestinal epithelial cells

Darine W. El-Naccache, Fei Chen, Mark J. Palma, Alexander Lemenze, Matthew A. Fischer, Wenhui Wu, Pankaj K. Mishra, Holger K. Eltzschig, Simon C. Robson, Francesco Di Virgilio, George S. Yap, Karen L. Edelblum, György Haskó, William C. Gause

Rutgers, The State University

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

Abstract

Intestinal nematode parasites can cross the epithelial barrier, causing tissue damage and release of danger-associated molecular patterns (DAMPs) that may promote host protective type 2 immunity. We investigate whether adenosine binding to the A_2B adenosine receptor (A_2BAR) on intestinal epithelial cells (IECs) plays an important role. Specific blockade of IEC A_2BAR inhibits the host protective memory response to the enteric helminth, Heligmosomoides polygyrus bakeri (Hpb), including disruption of granuloma development at the host-parasite interface. Memory T cell development is blocked during the primary response, and transcriptional analyses reveal profound impairment of IEC activation. Extracellular ATP is visualized 24 h after inoculation and is shown in CD39-deficient mice to be critical for the adenosine production mediating the initiation of type 2 immunity. Our studies indicate a potent adenosine-mediated IEC pathway that, along with the tuft cell circuit, is critical for the activation of type 2 immunity.

Original language	American English
Article number	111150
Journal	Cell Reports
Volume	40
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2022.111150
State	Published - Aug 2 2022

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Keywords

CP: Immunology
CP: Molecular biology

Access to Document

10.1016/j.celrep.2022.111150

Cite this

El-Naccache, D. W., Chen, F., Palma, M. J., Lemenze, A., Fischer, M. A., Wu, W., Mishra, P. K., Eltzschig, H. K., Robson, S. C., Di Virgilio, F., Yap, G. S., Edelblum, K. L., Haskó, G., & Gause, W. C. (2022). Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A_2BAR signaling in intestinal epithelial cells. Cell Reports, 40(5), Article 111150. https://doi.org/10.1016/j.celrep.2022.111150

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title = "Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A2BAR signaling in intestinal epithelial cells",

abstract = "Intestinal nematode parasites can cross the epithelial barrier, causing tissue damage and release of danger-associated molecular patterns (DAMPs) that may promote host protective type 2 immunity. We investigate whether adenosine binding to the A2B adenosine receptor (A2BAR) on intestinal epithelial cells (IECs) plays an important role. Specific blockade of IEC A2BAR inhibits the host protective memory response to the enteric helminth, Heligmosomoides polygyrus bakeri (Hpb), including disruption of granuloma development at the host-parasite interface. Memory T cell development is blocked during the primary response, and transcriptional analyses reveal profound impairment of IEC activation. Extracellular ATP is visualized 24 h after inoculation and is shown in CD39-deficient mice to be critical for the adenosine production mediating the initiation of type 2 immunity. Our studies indicate a potent adenosine-mediated IEC pathway that, along with the tuft cell circuit, is critical for the activation of type 2 immunity.",

keywords = "CP: Immunology, CP: Molecular biology",

author = "El-Naccache, {Darine W.} and Fei Chen and Palma, {Mark J.} and Alexander Lemenze and Fischer, {Matthew A.} and Wenhui Wu and Mishra, {Pankaj K.} and Eltzschig, {Holger K.} and Robson, {Simon C.} and {Di Virgilio}, Francesco and Yap, {George S.} and Edelblum, {Karen L.} and Gy{\"o}rgy Hask{\'o} and Gause, {William C.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = aug,

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doi = "10.1016/j.celrep.2022.111150",

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El-Naccache, DW, Chen, F, Palma, MJ, Lemenze, A, Fischer, MA, Wu, W, Mishra, PK, Eltzschig, HK, Robson, SC, Di Virgilio, F, Yap, GS, Edelblum, KL, Haskó, G & Gause, WC 2022, 'Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A_2BAR signaling in intestinal epithelial cells', Cell Reports, vol. 40, no. 5, 111150. https://doi.org/10.1016/j.celrep.2022.111150

TY - JOUR

T1 - Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A2BAR signaling in intestinal epithelial cells

AU - El-Naccache, Darine W.

AU - Chen, Fei

AU - Palma, Mark J.

AU - Lemenze, Alexander

AU - Fischer, Matthew A.

AU - Wu, Wenhui

AU - Mishra, Pankaj K.

AU - Eltzschig, Holger K.

AU - Robson, Simon C.

AU - Di Virgilio, Francesco

AU - Yap, George S.

AU - Edelblum, Karen L.

AU - Haskó, György

AU - Gause, William C.

PY - 2022/8/2

Y1 - 2022/8/2

N2 - Intestinal nematode parasites can cross the epithelial barrier, causing tissue damage and release of danger-associated molecular patterns (DAMPs) that may promote host protective type 2 immunity. We investigate whether adenosine binding to the A2B adenosine receptor (A2BAR) on intestinal epithelial cells (IECs) plays an important role. Specific blockade of IEC A2BAR inhibits the host protective memory response to the enteric helminth, Heligmosomoides polygyrus bakeri (Hpb), including disruption of granuloma development at the host-parasite interface. Memory T cell development is blocked during the primary response, and transcriptional analyses reveal profound impairment of IEC activation. Extracellular ATP is visualized 24 h after inoculation and is shown in CD39-deficient mice to be critical for the adenosine production mediating the initiation of type 2 immunity. Our studies indicate a potent adenosine-mediated IEC pathway that, along with the tuft cell circuit, is critical for the activation of type 2 immunity.

AB - Intestinal nematode parasites can cross the epithelial barrier, causing tissue damage and release of danger-associated molecular patterns (DAMPs) that may promote host protective type 2 immunity. We investigate whether adenosine binding to the A2B adenosine receptor (A2BAR) on intestinal epithelial cells (IECs) plays an important role. Specific blockade of IEC A2BAR inhibits the host protective memory response to the enteric helminth, Heligmosomoides polygyrus bakeri (Hpb), including disruption of granuloma development at the host-parasite interface. Memory T cell development is blocked during the primary response, and transcriptional analyses reveal profound impairment of IEC activation. Extracellular ATP is visualized 24 h after inoculation and is shown in CD39-deficient mice to be critical for the adenosine production mediating the initiation of type 2 immunity. Our studies indicate a potent adenosine-mediated IEC pathway that, along with the tuft cell circuit, is critical for the activation of type 2 immunity.

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KW - CP: Molecular biology

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