The STAT3–IL-10–IL-6 Pathway Is a Novel Regulator of Macrophage Efferocytosis and Phenotypic Conversion in Sterile Liver Injury

Lara Campana; Philip J Starkey Lewis; Antonella Pellicoro; Rebecca L Aucott; Janet Man; Eoghan O'Duibhir; Sarah E Mok; Sofia Ferreira-Gonzalez; Eilidh Livingstone; Stephen N Greenhalgh; Katherine L Hull; Douglas Vernimmen; Neil C Henderson; Luke Boulter; Christopher D Gregory; Yi Feng; Stephen M Anderton; Stuart J Forbes; John P Iredale

doi:10.4049/jimmunol.1701247

The STAT3–IL-10–IL-6 Pathway Is a Novel Regulator of Macrophage Efferocytosis and Phenotypic Conversion in Sterile Liver Injury

Lara Campana, Philip J Starkey Lewis, Antonella Pellicoro, Rebecca L Aucott, Janet Man, Eoghan O'Duibhir, Sarah E Mok, Sofia Ferreira-Gonzalez, Eilidh Livingstone, Stephen N Greenhalgh, Katherine L Hull, Douglas Vernimmen, Neil C Henderson, Luke Boulter, Christopher D Gregory, Yi Feng, Stephen M Anderton, Stuart J Forbes, John P Iredale

Research output: Contribution to journal › Article (Academic Journal) › peer-review

88 Citations (Scopus)

Abstract

The disposal of apoptotic bodies by professional phagocytes is crucial to effective inflammation resolution. Our ability to improve the disposal of apoptotic bodies by professional phagocytes is impaired by a limited understanding of the molecular mechanisms that regulate the engulfment and digestion of the efferocytic cargo. Macrophages are professional phagocytes necessary for liver inflammation, fibrosis, and resolution, switching their phenotype from proinflammatory to restorative. Using sterile liver injury models, we show that the STAT3–IL-10–IL-6 axis is a positive regulator of macrophage efferocytosis, survival, and phenotypic conversion, directly linking debris engulfment to tissue repair.

Original language	English
Pages (from-to)	1169-1187
Number of pages	19
Journal	Journal of Immunology
Volume	200
Issue number	3
Early online date	22 Jan 2018
DOIs	https://doi.org/10.4049/jimmunol.1701247
Publication status	Published - 1 Feb 2018

Bibliographical note

Keywords

Adoptive Transfer
Animals
Apoptosis/immunology
Humans
Interleukin-10/metabolism
Interleukin-6/metabolism
Liver/injuries
Liver Cirrhosis/pathology
Macrophages/immunology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Necrosis/immunology
Phagocytosis/immunology
Regeneration/physiology
STAT3 Transcription Factor/metabolism
Zebrafish/embryology

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Professor Sir John P Iredale
- john.iredalebristol.acuk
- Bristol Medical School - Professor of Experimental Medicine
- Cancer
Person: Academic , Member

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Campana, L., Starkey Lewis, P. J., Pellicoro, A., Aucott, R. L., Man, J., O'Duibhir, E., Mok, S. E., Ferreira-Gonzalez, S., Livingstone, E., Greenhalgh, S. N., Hull, K. L., Vernimmen, D., Henderson, N. C., Boulter, L., Gregory, C. D., Feng, Y., Anderton, S. M., Forbes, S. J., & Iredale, J. P. (2018). The STAT3–IL-10–IL-6 Pathway Is a Novel Regulator of Macrophage Efferocytosis and Phenotypic Conversion in Sterile Liver Injury. Journal of Immunology, 200(3), 1169-1187. https://doi.org/10.4049/jimmunol.1701247

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title = "The STAT3–IL-10–IL-6 Pathway Is a Novel Regulator of Macrophage Efferocytosis and Phenotypic Conversion in Sterile Liver Injury",

abstract = "The disposal of apoptotic bodies by professional phagocytes is crucial to effective inflammation resolution. Our ability to improve the disposal of apoptotic bodies by professional phagocytes is impaired by a limited understanding of the molecular mechanisms that regulate the engulfment and digestion of the efferocytic cargo. Macrophages are professional phagocytes necessary for liver inflammation, fibrosis, and resolution, switching their phenotype from proinflammatory to restorative. Using sterile liver injury models, we show that the STAT3–IL-10–IL-6 axis is a positive regulator of macrophage efferocytosis, survival, and phenotypic conversion, directly linking debris engulfment to tissue repair.",

keywords = "Adoptive Transfer, Animals, Apoptosis/immunology, Humans, Interleukin-10/metabolism, Interleukin-6/metabolism, Liver/injuries, Liver Cirrhosis/pathology, Macrophages/immunology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Necrosis/immunology, Phagocytosis/immunology, Regeneration/physiology, STAT3 Transcription Factor/metabolism, Zebrafish/embryology",

author = "Lara Campana and {Starkey Lewis}, {Philip J} and Antonella Pellicoro and Aucott, {Rebecca L} and Janet Man and Eoghan O'Duibhir and Mok, {Sarah E} and Sofia Ferreira-Gonzalez and Eilidh Livingstone and Greenhalgh, {Stephen N} and Hull, {Katherine L} and Douglas Vernimmen and Henderson, {Neil C} and Luke Boulter and Gregory, {Christopher D} and Yi Feng and Anderton, {Stephen M} and Forbes, {Stuart J} and Iredale, {John P}",

note = "Copyright {\textcopyright} 2018 by The American Association of Immunologists, Inc.",

year = "2018",

month = feb,

day = "1",

doi = "10.4049/jimmunol.1701247",

language = "English",

volume = "200",

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Campana, L, Starkey Lewis, PJ, Pellicoro, A, Aucott, RL, Man, J, O'Duibhir, E, Mok, SE, Ferreira-Gonzalez, S, Livingstone, E, Greenhalgh, SN, Hull, KL, Vernimmen, D, Henderson, NC, Boulter, L, Gregory, CD, Feng, Y, Anderton, SM, Forbes, SJ & Iredale, JP 2018, 'The STAT3–IL-10–IL-6 Pathway Is a Novel Regulator of Macrophage Efferocytosis and Phenotypic Conversion in Sterile Liver Injury', Journal of Immunology, vol. 200, no. 3, pp. 1169-1187. https://doi.org/10.4049/jimmunol.1701247

TY - JOUR

T1 - The STAT3–IL-10–IL-6 Pathway Is a Novel Regulator of Macrophage Efferocytosis and Phenotypic Conversion in Sterile Liver Injury

AU - Campana, Lara

AU - Starkey Lewis, Philip J

AU - Pellicoro, Antonella

AU - Aucott, Rebecca L

AU - Man, Janet

AU - O'Duibhir, Eoghan

AU - Mok, Sarah E

AU - Ferreira-Gonzalez, Sofia

AU - Livingstone, Eilidh

AU - Greenhalgh, Stephen N

AU - Hull, Katherine L

AU - Vernimmen, Douglas

AU - Henderson, Neil C

AU - Boulter, Luke

AU - Gregory, Christopher D

AU - Feng, Yi

AU - Anderton, Stephen M

AU - Forbes, Stuart J

AU - Iredale, John P

PY - 2018/2/1

Y1 - 2018/2/1

N2 - The disposal of apoptotic bodies by professional phagocytes is crucial to effective inflammation resolution. Our ability to improve the disposal of apoptotic bodies by professional phagocytes is impaired by a limited understanding of the molecular mechanisms that regulate the engulfment and digestion of the efferocytic cargo. Macrophages are professional phagocytes necessary for liver inflammation, fibrosis, and resolution, switching their phenotype from proinflammatory to restorative. Using sterile liver injury models, we show that the STAT3–IL-10–IL-6 axis is a positive regulator of macrophage efferocytosis, survival, and phenotypic conversion, directly linking debris engulfment to tissue repair.

AB - The disposal of apoptotic bodies by professional phagocytes is crucial to effective inflammation resolution. Our ability to improve the disposal of apoptotic bodies by professional phagocytes is impaired by a limited understanding of the molecular mechanisms that regulate the engulfment and digestion of the efferocytic cargo. Macrophages are professional phagocytes necessary for liver inflammation, fibrosis, and resolution, switching their phenotype from proinflammatory to restorative. Using sterile liver injury models, we show that the STAT3–IL-10–IL-6 axis is a positive regulator of macrophage efferocytosis, survival, and phenotypic conversion, directly linking debris engulfment to tissue repair.

KW - Adoptive Transfer

KW - Animals

KW - Apoptosis/immunology

KW - Humans

KW - Interleukin-10/metabolism

KW - Interleukin-6/metabolism

KW - Liver/injuries

KW - Liver Cirrhosis/pathology

KW - Macrophages/immunology

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Necrosis/immunology

KW - Phagocytosis/immunology

KW - Regeneration/physiology

KW - STAT3 Transcription Factor/metabolism

KW - Zebrafish/embryology

U2 - 10.4049/jimmunol.1701247

DO - 10.4049/jimmunol.1701247

M3 - Article (Academic Journal)

C2 - 29263216

SN - 0022-1767

VL - 200

SP - 1169

EP - 1187

JO - Journal of Immunology

JF - Journal of Immunology

IS - 3

ER -

The STAT3–IL-10–IL-6 Pathway Is a Novel Regulator of Macrophage Efferocytosis and Phenotypic Conversion in Sterile Liver Injury

Abstract

Bibliographical note

Keywords

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