Chronic inflammation in response to injury: retention of myeloid cells in injured tissue is driven by myeloid cell-intrinsic factorsCitation formats

  • External authors:
  • Tanja Torbica
  • Takahiro Umehara
  • Lale Gungordu
  • Salma Alrdahe
  • Kelly Wemyss
  • John Grainger

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Chronic inflammation in response to injury: retention of myeloid cells in injured tissue is driven by myeloid cell-intrinsic factors. / Torbica, Tanja; Wicks, Katherine; Umehara, Takahiro et al.

In: The Journal of Investigative Dermatology, 28.01.2019.

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@article{fc1751f6f37547c7a0dff925b8ae2087,
title = "Chronic inflammation in response to injury: retention of myeloid cells in injured tissue is driven by myeloid cell-intrinsic factors",
abstract = "Chronic inflammation is a hallmark of impaired healing in a plethora of tissues, including skin, and is associated with aging and diseases such as diabetes. Diabetic chronic skin wounds are characterized by excessive myeloid cells that display an aberrant phenotype, partially mediated by stable intrinsic changes induced during hematopoietic development.However, the relative contribution of myeloid cell-intrinsic factors to chronic inflammation versus aberrant signals from the local environmental was unknown. Moreover, identificationof myeloid cell-intrinsic factors that contribute to chronic inflammation in diabetic wounds remained elusive. Here we show that Gr-1+CD11b+ myeloid cells are retained specifically within the presumptive granulation tissue region of the wound at a higher density in diabetic mice and associate with endothelial cells at the site of injury with a higher frequency than innon-diabetic mice. Adoptive transfer of myeloid cells demonstrated that aberrant wound retention is due to myeloid cell-intrinsic factors and not the local environment. RNAsequencing of bone marrow and wound-derived myeloid cells identified Selplg as a myeloid cell-intrinsic factor that is deregulated in chronic wounds. In vivo blockade of this protein significantly accelerated wound healing in diabetic mice and may be a potential therapeutictarget in chronic wounds and other chronic inflammatory diseases. ",
author = "Tanja Torbica and Katherine Wicks and Takahiro Umehara and Lale Gungordu and Salma Alrdahe and Kelly Wemyss and John Grainger and Kimberly Mace",
year = "2019",
month = jan,
day = "28",
doi = "10.1016/j.jid.2018.12.030",
language = "English",
journal = "The Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Springer Nature",

}

RIS

TY - JOUR

T1 - Chronic inflammation in response to injury: retention of myeloid cells in injured tissue is driven by myeloid cell-intrinsic factors

AU - Torbica, Tanja

AU - Wicks, Katherine

AU - Umehara, Takahiro

AU - Gungordu, Lale

AU - Alrdahe, Salma

AU - Wemyss, Kelly

AU - Grainger, John

AU - Mace, Kimberly

PY - 2019/1/28

Y1 - 2019/1/28

N2 - Chronic inflammation is a hallmark of impaired healing in a plethora of tissues, including skin, and is associated with aging and diseases such as diabetes. Diabetic chronic skin wounds are characterized by excessive myeloid cells that display an aberrant phenotype, partially mediated by stable intrinsic changes induced during hematopoietic development.However, the relative contribution of myeloid cell-intrinsic factors to chronic inflammation versus aberrant signals from the local environmental was unknown. Moreover, identificationof myeloid cell-intrinsic factors that contribute to chronic inflammation in diabetic wounds remained elusive. Here we show that Gr-1+CD11b+ myeloid cells are retained specifically within the presumptive granulation tissue region of the wound at a higher density in diabetic mice and associate with endothelial cells at the site of injury with a higher frequency than innon-diabetic mice. Adoptive transfer of myeloid cells demonstrated that aberrant wound retention is due to myeloid cell-intrinsic factors and not the local environment. RNAsequencing of bone marrow and wound-derived myeloid cells identified Selplg as a myeloid cell-intrinsic factor that is deregulated in chronic wounds. In vivo blockade of this protein significantly accelerated wound healing in diabetic mice and may be a potential therapeutictarget in chronic wounds and other chronic inflammatory diseases.

AB - Chronic inflammation is a hallmark of impaired healing in a plethora of tissues, including skin, and is associated with aging and diseases such as diabetes. Diabetic chronic skin wounds are characterized by excessive myeloid cells that display an aberrant phenotype, partially mediated by stable intrinsic changes induced during hematopoietic development.However, the relative contribution of myeloid cell-intrinsic factors to chronic inflammation versus aberrant signals from the local environmental was unknown. Moreover, identificationof myeloid cell-intrinsic factors that contribute to chronic inflammation in diabetic wounds remained elusive. Here we show that Gr-1+CD11b+ myeloid cells are retained specifically within the presumptive granulation tissue region of the wound at a higher density in diabetic mice and associate with endothelial cells at the site of injury with a higher frequency than innon-diabetic mice. Adoptive transfer of myeloid cells demonstrated that aberrant wound retention is due to myeloid cell-intrinsic factors and not the local environment. RNAsequencing of bone marrow and wound-derived myeloid cells identified Selplg as a myeloid cell-intrinsic factor that is deregulated in chronic wounds. In vivo blockade of this protein significantly accelerated wound healing in diabetic mice and may be a potential therapeutictarget in chronic wounds and other chronic inflammatory diseases.

U2 - 10.1016/j.jid.2018.12.030

DO - 10.1016/j.jid.2018.12.030

M3 - Article

JO - The Journal of Investigative Dermatology

JF - The Journal of Investigative Dermatology

SN - 0022-202X

ER -