Efferocytosis fuels malignant pleural effusion through TIMP1

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Efferocytosis fuels malignant pleural effusion through TIMP1. / Zhao, Lilan; Giannou, Anastasios D.; Xu, Yang; Shiri, Ahmad Mustafa; Liebold, Imke; Steglich, Babett; Bedke, Tanja; Zhang, Tao; Lücke, Jöran; Scognamiglio, Pasquale; Kempski, Jan; Woestemeier, Anna; Chen, Jing; Agalioti, Theodora; Zazara, Dimitra E.; Lindner, Diana; Janning, Melanie; Hennigs, Jan K.; Jagirdar, Rajesh M.; Kotsiou, Ourania S.; Zarogiannis, Sotirios G.; Kobayashi, Yasushi; Izbicki, Jacob R.; Ghosh, Sourav; Rothlin, Carla V.; Bosurgi, Lidia; Huber, Samuel; Gagliani, Nicola.

In: SCI ADV, Vol. 7, No. 33, eabd6734, 08.2021.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

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Zhao, L, Giannou, AD, Xu, Y, Shiri, AM, Liebold, I, Steglich, B, Bedke, T, Zhang, T, Lücke, J, Scognamiglio, P, Kempski, J, Woestemeier, A, Chen, J, Agalioti, T, Zazara, DE, Lindner, D, Janning, M, Hennigs, JK, Jagirdar, RM, Kotsiou, OS, Zarogiannis, SG, Kobayashi, Y, Izbicki, JR, Ghosh, S, Rothlin, CV, Bosurgi, L, Huber, S & Gagliani, N 2021, 'Efferocytosis fuels malignant pleural effusion through TIMP1', SCI ADV, vol. 7, no. 33, eabd6734. https://doi.org/10.1126/sciadv.abd6734

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Bibtex

@article{a3a09a9b0eeb40fd89c05d889b13be84,
title = "Efferocytosis fuels malignant pleural effusion through TIMP1",
abstract = "Malignant pleural effusion (MPE) results from the capacity of several human cancers to metastasize to the pleural cavity. No effective treatments are currently available, reflecting our insufficient understanding of the basic mechanisms leading to MPE progression. Here, we found that efferocytosis through the receptor tyrosine kinases AXL and MERTK led to the production of interleukin-10 (IL-10) by four distinct pleural cavity macrophage (Mφ) subpopulations characterized by different metabolic states and cell chemotaxis properties. In turn, IL-10 acts on dendritic cells (DCs) inducing the production of tissue inhibitor of metalloproteinases 1 (TIMP1). Genetic ablation of Axl and Mertk in Mφs or IL-10 receptor in DCs or Timp1 substantially reduced MPE progression. Our results delineate an inflammatory cascade—from the clearance of apoptotic cells by Mφs, to production of IL-10, to induction of TIMP1 in DCs—that facilitates MPE progression. This inflammatory cascade offers a series of therapeutic targets for MPE.",
author = "Lilan Zhao and Giannou, {Anastasios D.} and Yang Xu and Shiri, {Ahmad Mustafa} and Imke Liebold and Babett Steglich and Tanja Bedke and Tao Zhang and J{\"o}ran L{\"u}cke and Pasquale Scognamiglio and Jan Kempski and Anna Woestemeier and Jing Chen and Theodora Agalioti and Zazara, {Dimitra E.} and Diana Lindner and Melanie Janning and Hennigs, {Jan K.} and Jagirdar, {Rajesh M.} and Kotsiou, {Ourania S.} and Zarogiannis, {Sotirios G.} and Yasushi Kobayashi and Izbicki, {Jacob R.} and Sourav Ghosh and Rothlin, {Carla V.} and Lidia Bosurgi and Samuel Huber and Nicola Gagliani",
note = "Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved.",
year = "2021",
month = aug,
doi = "10.1126/sciadv.abd6734",
language = "English",
volume = "7",
journal = "SCI ADV",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "33",

}

RIS

TY - JOUR

T1 - Efferocytosis fuels malignant pleural effusion through TIMP1

AU - Zhao, Lilan

AU - Giannou, Anastasios D.

AU - Xu, Yang

AU - Shiri, Ahmad Mustafa

AU - Liebold, Imke

AU - Steglich, Babett

AU - Bedke, Tanja

AU - Zhang, Tao

AU - Lücke, Jöran

AU - Scognamiglio, Pasquale

AU - Kempski, Jan

AU - Woestemeier, Anna

AU - Chen, Jing

AU - Agalioti, Theodora

AU - Zazara, Dimitra E.

AU - Lindner, Diana

AU - Janning, Melanie

AU - Hennigs, Jan K.

AU - Jagirdar, Rajesh M.

AU - Kotsiou, Ourania S.

AU - Zarogiannis, Sotirios G.

AU - Kobayashi, Yasushi

AU - Izbicki, Jacob R.

AU - Ghosh, Sourav

AU - Rothlin, Carla V.

AU - Bosurgi, Lidia

AU - Huber, Samuel

AU - Gagliani, Nicola

N1 - Publisher Copyright: Copyright © 2021 The Authors, some rights reserved.

PY - 2021/8

Y1 - 2021/8

N2 - Malignant pleural effusion (MPE) results from the capacity of several human cancers to metastasize to the pleural cavity. No effective treatments are currently available, reflecting our insufficient understanding of the basic mechanisms leading to MPE progression. Here, we found that efferocytosis through the receptor tyrosine kinases AXL and MERTK led to the production of interleukin-10 (IL-10) by four distinct pleural cavity macrophage (Mφ) subpopulations characterized by different metabolic states and cell chemotaxis properties. In turn, IL-10 acts on dendritic cells (DCs) inducing the production of tissue inhibitor of metalloproteinases 1 (TIMP1). Genetic ablation of Axl and Mertk in Mφs or IL-10 receptor in DCs or Timp1 substantially reduced MPE progression. Our results delineate an inflammatory cascade—from the clearance of apoptotic cells by Mφs, to production of IL-10, to induction of TIMP1 in DCs—that facilitates MPE progression. This inflammatory cascade offers a series of therapeutic targets for MPE.

AB - Malignant pleural effusion (MPE) results from the capacity of several human cancers to metastasize to the pleural cavity. No effective treatments are currently available, reflecting our insufficient understanding of the basic mechanisms leading to MPE progression. Here, we found that efferocytosis through the receptor tyrosine kinases AXL and MERTK led to the production of interleukin-10 (IL-10) by four distinct pleural cavity macrophage (Mφ) subpopulations characterized by different metabolic states and cell chemotaxis properties. In turn, IL-10 acts on dendritic cells (DCs) inducing the production of tissue inhibitor of metalloproteinases 1 (TIMP1). Genetic ablation of Axl and Mertk in Mφs or IL-10 receptor in DCs or Timp1 substantially reduced MPE progression. Our results delineate an inflammatory cascade—from the clearance of apoptotic cells by Mφs, to production of IL-10, to induction of TIMP1 in DCs—that facilitates MPE progression. This inflammatory cascade offers a series of therapeutic targets for MPE.

UR - http://www.scopus.com/inward/record.url?scp=85112562444&partnerID=8YFLogxK

U2 - 10.1126/sciadv.abd6734

DO - 10.1126/sciadv.abd6734

M3 - SCORING: Journal article

C2 - 34389533

AN - SCOPUS:85112562444

VL - 7

JO - SCI ADV

JF - SCI ADV

SN - 2375-2548

IS - 33

M1 - eabd6734

ER -