The significance of M1-polarized CD163+ macrophages in acute graft-versus-host disease (GVHD): Possible mechanisms of GVHD in the development of skin lesions

IF 1.1 Q4 ALLERGY
Yusuke Muto MD, PhD, Taku Fujimura MD, PhD, Yumi Kambayashi MD, PhD, Kentaro Ohuchi MD, PhD, Chunbing Lyu MD, PhD, Hitoshi Terui MD, PhD, Masato Mizuashi MD, PhD, Setsuya Aiba MD, PhD, Yoshihide Asano MD, PhD
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Abstract

Objectives

Graft-versus-host disease (GVHD) is an important complication of bone marrow transplantation. Recent reports suggest the significance of T-cell subsets (Th1, Th17, and cytotoxic CD8+ T cells) as well as CD163+ macrophages in the development of cutaneous GVHD. CD163+ macrophages produce various chemokines to establish the immunological microenvironment following stimulation by stromal factors in lesional skin. Thus, the purpose of this study is to determine the main source of IFN-inducible chemokines in the lesional skin of GVHD.

Methods

We employed immunohistochemical (IHC) staining for CD163 as well as interferon (IFN)-inducible chemokines (CXCL9, CXCL10, CXCL11) to determine if the main source of IFN-inducible chemokines in the lesional skin of GVHD was CD163+ macrophages. Moreover, we investigated the possible cytokine profiles of lesional skin in GVHD by evaluating phospho-signal transducer and activator of transcription (pSTAT) expression in epidermal keratinocytes.

Results

Immunohistochemical staining of serial sections for CD163 revealed that CXCL9-expressing cells, CXCL10-expressing cells, and CXCL11-expressing cells were detected in adjacent to CD163+ TAMs in the dermis. In contrast, there were no CCL17-expressing cells or CCL22-expressing cells in the dermis. The nuclei of epidermal keratinocytes in GVHD expressed pSTAT1, pSTAT3, and pSTAT5B.

Conclusions

The chemokine expression patterns on CD163+ macrophages matched the expected phosphorylation pattern of epidermal STATs. Our present study suggested that CD163 + macrophages may be a therapeutic target in GVHD.

Abstract Image

M1极化CD163+巨噬细胞在急性移植物抗宿主病(GVHD)中的意义:GVHD在皮肤病变发展中的可能机制
移植物抗宿主病(GVHD)是骨髓移植的一个重要并发症。最近的报告表明,T细胞亚群(Th1、Th17和细胞毒性CD8+T细胞)以及CD163+巨噬细胞在皮肤移植物抗宿主病的发展中具有重要意义。CD163+巨噬细胞在病变皮肤中受到基质因子的刺激后产生各种趋化因子以建立免疫微环境。因此,本研究的目的是确定移植物抗宿主病病变皮肤中IFN-诱导的趋化因子的主要来源。
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来源期刊
CiteScore
0.60
自引率
10.00%
发文量
69
审稿时长
12 weeks
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