Chronic Inflammation in Response to Injury: Retention of Myeloid Cells in Injured Tissue Is Driven by Myeloid Cell Intrinsic Factors

Published on Jul 1, 2019in Journal of Investigative Dermatology7.143
· DOI :10.1016/J.JID.2018.12.030
Tanja Torbica3
Estimated H-index: 3
(University of Manchester),
Kate Wicks9
Estimated H-index: 9
(University of Manchester)
+ 5 AuthorsKimberly A. Mace16
Estimated H-index: 16
(University of Manchester)
Sources
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, identification of 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 in nondiabetic mice. Adoptive transfer of myeloid cells demonstrated that aberrant wound retention is due to myeloid cell intrinsic factors and not the local environment. RNA sequencing 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 therapeutic target in chronic wounds and other chronic inflammatory diseases.
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