Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation

Laurel A. Monticelli; Michael D. Buck; Anne Laure Flamar; Steven A. Saenz; Elia D.Tait Wojno; Naomi A. Yudanin; Lisa C. Osborne; Matthew R. Hepworth; Sara V. Tran; Hans Reimer Rodewald; Hardik Shah; Justin R. Cross; Joshua M. Diamond; Edward Cantu; Jason D. Christie; Erika L. Pearce; David Artis

doi:10.1038/ni.3421

Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation

Laurel A. Monticelli
, Michael D. Buck
, Anne Laure Flamar
, Steven A. Saenz
, Elia D.Tait Wojno
, Naomi A. Yudanin
, Lisa C. Osborne
, Matthew R. Hepworth
, Sara V. Tran
, Hans Reimer Rodewald
, Hardik Shah
, Justin R. Cross
, Joshua M. Diamond
, Edward Cantu
, Jason D. Christie
, Erika L. Pearce
, David Artis

Surgery

Producción científica: Article › revisión exhaustiva

259 Citas (Scopus)

Resumen

Group 2 innate lymphoid cells (ILC2s) regulate tissue inflammation and repair after activation by cell-extrinsic factors such as host-derived cytokines. However, the cell-intrinsic metabolic pathways that control ILC2 function are undefined. Here we demonstrate that expression of the enzyme arginase-1 (Arg1) during acute or chronic lung inflammation is a conserved trait of mouse and human ILC2s. Deletion of mouse ILC-intrinsic Arg1 abrogated type 2 lung inflammation by restraining ILC2 proliferation and dampening cytokine production. Mechanistically, inhibition of Arg1 enzymatic activity disrupted multiple components of ILC2 metabolic programming by altering arginine catabolism, impairing polyamine biosynthesis and reducing aerobic glycolysis. These data identify Arg1 as a key regulator of ILC2 bioenergetics that controls proliferative capacity and proinflammatory functions promoting type 2 inflammation.

Idioma original	English
Páginas (desde-hasta)	656-665
Número de páginas	10
Publicación	Nature Immunology
Volumen	17
N.º	6
DOI	https://doi.org/10.1038/ni.3421
Estado	Published - may 19 2016

Nota bibliográfica

Publisher Copyright:
© 2016 Nature America, Inc.

Financiación

We thank members of the D. Artis and G.F. Sonnenberg laboratories for critical reading of this manuscript. We thank R.M. Locksley (University of California, San Francisco, San Francisco, California, USA) for generously providing the Arg1YFP mice and B. Vallance (University of British Columbia, Vancouver, British Columbia, Canada) for providing Citrobacter rodentium. This work was supported by the National Institutes of Health (NIH) (grants AI061570, AI087990, AI074878, AI083480, AI095466, AI095608, AI102942 and AI097333 to D.A.; T32-AI007532 to L.A.M.; CA181125 and AI091965 to E.L.P.; HL087115, HL081619, HL096845, HL115354 and HL114626 to J.D.C.; HL116656 to E.C.; and HL090021 and K23-HL121406 to J.M.D.), the Burroughs Wellcome Fund (D.A. and E.L.P.), the Crohn's & Colitis Foundation of America (D.A. and M.R.H.), the Edmond J. Safra Foundation/Cancer Research Institute (L.C.O.), the National Science Foundation (grant DGE-1143954 to M.D.B.), the Robert Wood Johnson Foundation (grant AMFDP 70640 to E.C.), the Thoracic Surgery Foundation (E.C.) and the German Research Foundation (DFG SFB 873project 11 to H.-R.R.). We thank the Mucosal Immunology Studies Team (MIST) of the NIH NIAID for shared expertise and resources.

Financiadores	Número del financiador
D. Artis
Edmond J. Safra Foundation/Cancer Research Institute
National Science Foundation Arctic Social Science Program	DGE-1143954
National Institutes of Health (NIH)	AI061570, AI083480, AI102942, AI087990, HL096845, CA181125, AI095466, T32-AI007532, K23-HL121406, AI091965, AI074878, HL087115, HL116656, AI097333, HL115354, HL081619, HL090021, HL114626
National Institute of Allergy and Infectious F32-AI286447 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI168214 Jason W. Rosch Diseases National Institute of Allergy and Infectious P30 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R00-AI166116 Christopher D. Radka Diseases National Institute of Allergy and Infectious T32-AI106700 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI192221 Jason W. Rosch Diseases National Inst...	U01AI095608
Burroughs Wellcome Fund
Robert Wood Johnson Foundation	AMFDP 70640
Crohn's and Colitis Foundation of America
Thoracic Surgery Foundation
Deutsche Forschungsgemeinschaft	SFB 873project 11
Univ. of Northern British Columbia

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1038/ni.3421

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Monticelli, L. A., Buck, M. D., Flamar, A. L., Saenz, S. A., Wojno, E. D. T., Yudanin, N. A., Osborne, L. C., Hepworth, M. R., Tran, S. V., Rodewald, H. R., Shah, H., Cross, J. R., Diamond, J. M., Cantu, E., Christie, J. D., Pearce, E. L., & Artis, D. (2016). Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation. Nature Immunology, 17(6), 656-665. https://doi.org/10.1038/ni.3421

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title = "Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation",

abstract = "Group 2 innate lymphoid cells (ILC2s) regulate tissue inflammation and repair after activation by cell-extrinsic factors such as host-derived cytokines. However, the cell-intrinsic metabolic pathways that control ILC2 function are undefined. Here we demonstrate that expression of the enzyme arginase-1 (Arg1) during acute or chronic lung inflammation is a conserved trait of mouse and human ILC2s. Deletion of mouse ILC-intrinsic Arg1 abrogated type 2 lung inflammation by restraining ILC2 proliferation and dampening cytokine production. Mechanistically, inhibition of Arg1 enzymatic activity disrupted multiple components of ILC2 metabolic programming by altering arginine catabolism, impairing polyamine biosynthesis and reducing aerobic glycolysis. These data identify Arg1 as a key regulator of ILC2 bioenergetics that controls proliferative capacity and proinflammatory functions promoting type 2 inflammation.",

author = "Monticelli, \{Laurel A.\} and Buck, \{Michael D.\} and Flamar, \{Anne Laure\} and Saenz, \{Steven A.\} and Wojno, \{Elia D.Tait\} and Yudanin, \{Naomi A.\} and Osborne, \{Lisa C.\} and Hepworth, \{Matthew R.\} and Tran, \{Sara V.\} and Rodewald, \{Hans Reimer\} and Hardik Shah and Cross, \{Justin R.\} and Diamond, \{Joshua M.\} and Edward Cantu and Christie, \{Jason D.\} and Pearce, \{Erika L.\} and David Artis",

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year = "2016",

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doi = "10.1038/ni.3421",

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Monticelli, LA, Buck, MD, Flamar, AL, Saenz, SA, Wojno, EDT, Yudanin, NA, Osborne, LC, Hepworth, MR, Tran, SV, Rodewald, HR, Shah, H, Cross, JR, Diamond, JM, Cantu, E, Christie, JD, Pearce, EL & Artis, D 2016, 'Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation', Nature Immunology, vol. 17, n.º 6, pp. 656-665. https://doi.org/10.1038/ni.3421

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AU - Rodewald, Hans Reimer

AU - Shah, Hardik

AU - Cross, Justin R.

AU - Diamond, Joshua M.

AU - Cantu, Edward

AU - Christie, Jason D.

AU - Pearce, Erika L.

AU - Artis, David

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AB - Group 2 innate lymphoid cells (ILC2s) regulate tissue inflammation and repair after activation by cell-extrinsic factors such as host-derived cytokines. However, the cell-intrinsic metabolic pathways that control ILC2 function are undefined. Here we demonstrate that expression of the enzyme arginase-1 (Arg1) during acute or chronic lung inflammation is a conserved trait of mouse and human ILC2s. Deletion of mouse ILC-intrinsic Arg1 abrogated type 2 lung inflammation by restraining ILC2 proliferation and dampening cytokine production. Mechanistically, inhibition of Arg1 enzymatic activity disrupted multiple components of ILC2 metabolic programming by altering arginine catabolism, impairing polyamine biosynthesis and reducing aerobic glycolysis. These data identify Arg1 as a key regulator of ILC2 bioenergetics that controls proliferative capacity and proinflammatory functions promoting type 2 inflammation.

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Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation

Resumen

Nota bibliográfica

Financiación

ASJC Scopus subject areas

Acceder al documento

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