DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas. / Herrtwich, Laura; Nanda, Indrajit; Evangelou, Konstantinos; Nikolova, Teodora; Horn, Veronika; Sagar; Erny, Daniel; Stefanowski, Jonathan; Rogell, Leif; Klein, Claudius; Gharun, Kourosh; Follo, Marie; Seidl, Maximilian; Kremer, Bernhard; Muenke, Nikolas; Senges, Julia; Fliegauf, Manfred; Aschman, Tom; Pfeifer, Dietmar; Sarrazin, Sandrine; Sieweke, Michael H.; Wagner, Dirk; Dierks, Christine; Haaf, Thomas; Ness, Thomas; Zaiss, Mario M.; Voll, Reinhard E.; Deshmukh, Sachin D.; Prinz, Marco; Goldmann, Torsten; Hoelscher, Christoph; Hauser, Anja E.; Lopez-Contreras, Andres J.; Gruen, Dominic; Gorgoulis, Vassilis; Diefenbach, Andreas; Henneke, Philipp; Triantafyllopoulou, Antigoni.

In: Cell, Vol. 167, No. 5, 17.11.2016, p. 1264–1280.e18.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Herrtwich, L, Nanda, I, Evangelou, K, Nikolova, T, Horn, V, Sagar, Erny, D, Stefanowski, J, Rogell, L, Klein, C, Gharun, K, Follo, M, Seidl, M, Kremer, B, Muenke, N, Senges, J, Fliegauf, M, Aschman, T, Pfeifer, D, Sarrazin, S, Sieweke, MH, Wagner, D, Dierks, C, Haaf, T, Ness, T, Zaiss, MM, Voll, RE, Deshmukh, SD, Prinz, M, Goldmann, T, Hoelscher, C, Hauser, AE, Lopez-Contreras, AJ, Gruen, D, Gorgoulis, V, Diefenbach, A, Henneke, P & Triantafyllopoulou, A 2016, 'DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas', Cell, vol. 167, no. 5, pp. 1264–1280.e18. https://doi.org/10.1016/j.cell.2016.09.054

APA

Herrtwich, L., Nanda, I., Evangelou, K., Nikolova, T., Horn, V., Sagar, Erny, D., Stefanowski, J., Rogell, L., Klein, C., Gharun, K., Follo, M., Seidl, M., Kremer, B., Muenke, N., Senges, J., Fliegauf, M., Aschman, T., Pfeifer, D., ... Triantafyllopoulou, A. (2016). DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas. Cell, 167(5), 1264–1280.e18. https://doi.org/10.1016/j.cell.2016.09.054

Vancouver

Herrtwich L, Nanda I, Evangelou K, Nikolova T, Horn V, Sagar et al. DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas. Cell. 2016 Nov 17;167(5):1264–1280.e18. https://doi.org/10.1016/j.cell.2016.09.054

Author

Herrtwich, Laura ; Nanda, Indrajit ; Evangelou, Konstantinos ; Nikolova, Teodora ; Horn, Veronika ; Sagar ; Erny, Daniel ; Stefanowski, Jonathan ; Rogell, Leif ; Klein, Claudius ; Gharun, Kourosh ; Follo, Marie ; Seidl, Maximilian ; Kremer, Bernhard ; Muenke, Nikolas ; Senges, Julia ; Fliegauf, Manfred ; Aschman, Tom ; Pfeifer, Dietmar ; Sarrazin, Sandrine ; Sieweke, Michael H. ; Wagner, Dirk ; Dierks, Christine ; Haaf, Thomas ; Ness, Thomas ; Zaiss, Mario M. ; Voll, Reinhard E. ; Deshmukh, Sachin D. ; Prinz, Marco ; Goldmann, Torsten ; Hoelscher, Christoph ; Hauser, Anja E. ; Lopez-Contreras, Andres J. ; Gruen, Dominic ; Gorgoulis, Vassilis ; Diefenbach, Andreas ; Henneke, Philipp ; Triantafyllopoulou, Antigoni. / DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas. In: Cell. 2016 ; Vol. 167, No. 5. pp. 1264–1280.e18.

Bibtex

@article{34bce7cba03b4c2d974d5633220e4db9,
title = "DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas",
abstract = "Granulomas are immune cell aggregates formed in response to persistent inflammatory stimuli. Granuloma macrophage subsets are diverse and carry varying copy numbers of their genomic information. The molecular programs that control the differentiation of such macrophage populations in response to a chronic stimulus, though critical for disease outcome, have not been defined. Here, we delineate a macrophage differentiation pathway by which a persistent Toll-like receptor (TLR) 2 signal instructs polyploid macrophage fate by inducing replication stress and activating the DNA damage response. Polyploid granuloma-resident macrophages formed via modified cell divisions and mitotic defects and not, as previously thought, by cell-to-cell fusion. TLR2 signaling promoted macrophage polyploidy and suppressed genomic instability by regulating Myc and ATR. We propose that, in the presence of persistent inflammatory stimuli, pathways previously linked to oncogene-initiated carcinogenesis instruct a long-lived granuloma-resident macrophage differentiation program that regulates granulomatous tissue remodeling.",
author = "Laura Herrtwich and Indrajit Nanda and Konstantinos Evangelou and Teodora Nikolova and Veronika Horn and Sagar and Daniel Erny and Jonathan Stefanowski and Leif Rogell and Claudius Klein and Kourosh Gharun and Marie Follo and Maximilian Seidl and Bernhard Kremer and Nikolas Muenke and Julia Senges and Manfred Fliegauf and Tom Aschman and Dietmar Pfeifer and Sandrine Sarrazin and Sieweke, {Michael H.} and Dirk Wagner and Christine Dierks and Thomas Haaf and Thomas Ness and Zaiss, {Mario M.} and Voll, {Reinhard E.} and Deshmukh, {Sachin D.} and Marco Prinz and Torsten Goldmann and Christoph Hoelscher and Hauser, {Anja E.} and Lopez-Contreras, {Andres J.} and Dominic Gruen and Vassilis Gorgoulis and Andreas Diefenbach and Philipp Henneke and Antigoni Triantafyllopoulou",
year = "2016",
month = nov,
day = "17",
doi = "10.1016/j.cell.2016.09.054",
language = "English",
volume = "167",
pages = "1264–1280.e18",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",

}

RIS

TY - JOUR

T1 - DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas

AU - Herrtwich, Laura

AU - Nanda, Indrajit

AU - Evangelou, Konstantinos

AU - Nikolova, Teodora

AU - Horn, Veronika

AU - Sagar, null

AU - Erny, Daniel

AU - Stefanowski, Jonathan

AU - Rogell, Leif

AU - Klein, Claudius

AU - Gharun, Kourosh

AU - Follo, Marie

AU - Seidl, Maximilian

AU - Kremer, Bernhard

AU - Muenke, Nikolas

AU - Senges, Julia

AU - Fliegauf, Manfred

AU - Aschman, Tom

AU - Pfeifer, Dietmar

AU - Sarrazin, Sandrine

AU - Sieweke, Michael H.

AU - Wagner, Dirk

AU - Dierks, Christine

AU - Haaf, Thomas

AU - Ness, Thomas

AU - Zaiss, Mario M.

AU - Voll, Reinhard E.

AU - Deshmukh, Sachin D.

AU - Prinz, Marco

AU - Goldmann, Torsten

AU - Hoelscher, Christoph

AU - Hauser, Anja E.

AU - Lopez-Contreras, Andres J.

AU - Gruen, Dominic

AU - Gorgoulis, Vassilis

AU - Diefenbach, Andreas

AU - Henneke, Philipp

AU - Triantafyllopoulou, Antigoni

PY - 2016/11/17

Y1 - 2016/11/17

N2 - Granulomas are immune cell aggregates formed in response to persistent inflammatory stimuli. Granuloma macrophage subsets are diverse and carry varying copy numbers of their genomic information. The molecular programs that control the differentiation of such macrophage populations in response to a chronic stimulus, though critical for disease outcome, have not been defined. Here, we delineate a macrophage differentiation pathway by which a persistent Toll-like receptor (TLR) 2 signal instructs polyploid macrophage fate by inducing replication stress and activating the DNA damage response. Polyploid granuloma-resident macrophages formed via modified cell divisions and mitotic defects and not, as previously thought, by cell-to-cell fusion. TLR2 signaling promoted macrophage polyploidy and suppressed genomic instability by regulating Myc and ATR. We propose that, in the presence of persistent inflammatory stimuli, pathways previously linked to oncogene-initiated carcinogenesis instruct a long-lived granuloma-resident macrophage differentiation program that regulates granulomatous tissue remodeling.

AB - Granulomas are immune cell aggregates formed in response to persistent inflammatory stimuli. Granuloma macrophage subsets are diverse and carry varying copy numbers of their genomic information. The molecular programs that control the differentiation of such macrophage populations in response to a chronic stimulus, though critical for disease outcome, have not been defined. Here, we delineate a macrophage differentiation pathway by which a persistent Toll-like receptor (TLR) 2 signal instructs polyploid macrophage fate by inducing replication stress and activating the DNA damage response. Polyploid granuloma-resident macrophages formed via modified cell divisions and mitotic defects and not, as previously thought, by cell-to-cell fusion. TLR2 signaling promoted macrophage polyploidy and suppressed genomic instability by regulating Myc and ATR. We propose that, in the presence of persistent inflammatory stimuli, pathways previously linked to oncogene-initiated carcinogenesis instruct a long-lived granuloma-resident macrophage differentiation program that regulates granulomatous tissue remodeling.

U2 - 10.1016/j.cell.2016.09.054

DO - 10.1016/j.cell.2016.09.054

M3 - Journal article

C2 - 28084216

VL - 167

SP - 1264–1280.e18

JO - Cell

JF - Cell

SN - 0092-8674

IS - 5

ER -

ID: 170737072