CD64 plays a key role in diabetic wound healing

IntroductionWound healing poses a clinical challenge in diabetes mellitus (DM) due to compromised host immunity. CD64, an IgG-binding Fcgr1 receptor, acts as a pro-inflammatory mediator. While its presence has been identified in various inflammatory diseases, its specific role in wound healing, espe...

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Main Authors: Xiuqin Zhang, Liuhong Yuan, Zhenyu Tan, Huiyan Wu, Feier Chen, Junjie Huang, Pengjun Wang, Brett D. Hambly, Shisan Bao, Kun Tao
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1322256/full
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author Xiuqin Zhang
Liuhong Yuan
Zhenyu Tan
Huiyan Wu
Feier Chen
Junjie Huang
Pengjun Wang
Brett D. Hambly
Shisan Bao
Kun Tao
author_facet Xiuqin Zhang
Liuhong Yuan
Zhenyu Tan
Huiyan Wu
Feier Chen
Junjie Huang
Pengjun Wang
Brett D. Hambly
Shisan Bao
Kun Tao
author_sort Xiuqin Zhang
collection DOAJ
description IntroductionWound healing poses a clinical challenge in diabetes mellitus (DM) due to compromised host immunity. CD64, an IgG-binding Fcgr1 receptor, acts as a pro-inflammatory mediator. While its presence has been identified in various inflammatory diseases, its specific role in wound healing, especially in DM, remains unclear.ObjectivesWe aimed to investigate the involvement of CD64 in diabetic wound healing using a DM animal model with CD64 KO mice.MethodsFirst, we compared CD64 expression in chronic skin ulcers from human DM and non-DM skin. Then, we monitored wound healing in a DM mouse model over 10 days, with or without CD64 KO, using macroscopic and microscopic observations, as well as immunohistochemistry.ResultsCD64 expression was significantly upregulated (1.25-fold) in chronic ulcerative skin from DM patients compared to non-DM individuals. Clinical observations were consistent with animal model findings, showing a significant delay in wound healing, particularly by day 7, in CD64 KO mice compared to WT mice. Additionally, infiltrating CD163+ M2 macrophages in the wounds of DM mice decreased significantly compared to non-DM mice over time. Delayed wound healing in DM CD64 KO mice correlated with the presence of inflammatory mediators.ConclusionCD64 seems to play a crucial role in wound healing, especially in DM conditions, where it is associated with CD163+ M2 macrophage infiltration. These data suggest that CD64 relies on host immunity during the wound healing process. Such data may provide useful information for both basic scientists and clinicians to deal with diabetic chronic wound healing.
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spelling doaj.art-835c97946d8749359e3eb9ae22ccd3ed2024-03-08T04:34:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13222561322256CD64 plays a key role in diabetic wound healingXiuqin Zhang0Liuhong Yuan1Zhenyu Tan2Huiyan Wu3Feier Chen4Junjie Huang5Pengjun Wang6Brett D. Hambly7Shisan Bao8Kun Tao9Department of Pathology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Pathology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Pathology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Pathology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Pathology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Pathology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Pathology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Pathology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Pathology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Pathology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, ChinaIntroductionWound healing poses a clinical challenge in diabetes mellitus (DM) due to compromised host immunity. CD64, an IgG-binding Fcgr1 receptor, acts as a pro-inflammatory mediator. While its presence has been identified in various inflammatory diseases, its specific role in wound healing, especially in DM, remains unclear.ObjectivesWe aimed to investigate the involvement of CD64 in diabetic wound healing using a DM animal model with CD64 KO mice.MethodsFirst, we compared CD64 expression in chronic skin ulcers from human DM and non-DM skin. Then, we monitored wound healing in a DM mouse model over 10 days, with or without CD64 KO, using macroscopic and microscopic observations, as well as immunohistochemistry.ResultsCD64 expression was significantly upregulated (1.25-fold) in chronic ulcerative skin from DM patients compared to non-DM individuals. Clinical observations were consistent with animal model findings, showing a significant delay in wound healing, particularly by day 7, in CD64 KO mice compared to WT mice. Additionally, infiltrating CD163+ M2 macrophages in the wounds of DM mice decreased significantly compared to non-DM mice over time. Delayed wound healing in DM CD64 KO mice correlated with the presence of inflammatory mediators.ConclusionCD64 seems to play a crucial role in wound healing, especially in DM conditions, where it is associated with CD163+ M2 macrophage infiltration. These data suggest that CD64 relies on host immunity during the wound healing process. Such data may provide useful information for both basic scientists and clinicians to deal with diabetic chronic wound healing.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1322256/fulldiabetes mellitusCD64CD163+ M2 macrophagewound healingCD68/CD80 M1 macrophages
spellingShingle Xiuqin Zhang
Liuhong Yuan
Zhenyu Tan
Huiyan Wu
Feier Chen
Junjie Huang
Pengjun Wang
Brett D. Hambly
Shisan Bao
Kun Tao
CD64 plays a key role in diabetic wound healing
Frontiers in Immunology
diabetes mellitus
CD64
CD163+ M2 macrophage
wound healing
CD68/CD80 M1 macrophages
title CD64 plays a key role in diabetic wound healing
title_full CD64 plays a key role in diabetic wound healing
title_fullStr CD64 plays a key role in diabetic wound healing
title_full_unstemmed CD64 plays a key role in diabetic wound healing
title_short CD64 plays a key role in diabetic wound healing
title_sort cd64 plays a key role in diabetic wound healing
topic diabetes mellitus
CD64
CD163+ M2 macrophage
wound healing
CD68/CD80 M1 macrophages
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1322256/full
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