FcγRIIB 在小鼠博来霉素诱导性纤维化中的作用。

A role for FcγRIIB in the development of murine bleomycin-induced fibrosis.

机构信息

Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.

出版信息

J Dermatol Sci. 2021 Dec;104(3):201-209. doi: 10.1016/j.jdermsci.2021.11.002. Epub 2021 Nov 9.

DOI:10.1016/j.jdermsci.2021.11.002

PMID:34844843

Abstract

BACKGROUND

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by excessive fibrosis. FcγRIIB is a low-affinity receptor for the Fc fragment of IgG. FcγRIIB is expressed on the surface of various leukocyte subsets and signals negative feedback pathways to down-regulate B-cell antigen receptor signaling.

OBJECTIVE

The aim of the present study was to investigate the role of FcγRIIB in the development of a murine bleomycin-induced scleroderma model.

METHODS

The experimental fibrosis model was generated by the intradermal injection of bleomycin into wild-type (WT) and FcγRIIB-deficient (FcγRIIB) mice. We histologically assessed skin and lung fibrosis as well as inflammatory cell infiltration. Cytokine and chemokine expression levels were measured with RT-PCR.

RESULTS

The severity of fibrosis in the skin and lung was significantly worse in FcγRIIB mice than in WT mice. In the skin of bleomycin-treated mice, the numbers of CD8 T cells, F4/80 macrophages, MPO neutrophils, NK1.1NK cells, and B220 B cells were significantly higher in FcγRIIB mice than in WT mice. The expression of TNF-α and IL-1β was significantly higher in FcγRIIB mice than in WT mice as was the expression of ICAM-1, CXCL2, and CCL3 in the affected skin. An adoptive transfer of splenic leukocytes from FcγRIIB mice into WT mice showed exacerbated skin and lung fibrosis compared to WT mice without an adoptive transfer.

CONCLUSION

These results indicate that FcγRIIB plays an inhibitory role in skin and lung fibrosis. Moreover, modulating FcγRIIB signaling has potential as a therapeutic approach for SSc.

摘要

背景

系统性硬化症（SSc）是一种以过度纤维化为特征的系统性自身免疫性疾病。FcγRIIB 是 IgG Fc 片段的低亲和力受体。FcγRIIB 表达于各种白细胞亚群的表面，并通过信号负反馈途径下调 B 细胞抗原受体信号。

目的

本研究旨在探讨 FcγRIIB 在小鼠博来霉素诱导的硬皮病模型中的作用。

方法

通过将博来霉素皮内注射到野生型（WT）和 FcγRIIB 缺陷型（FcγRIIB）小鼠中，建立实验性纤维化模型。我们通过组织学评估皮肤和肺纤维化以及炎症细胞浸润。用 RT-PCR 测量细胞因子和趋化因子的表达水平。

结果

FcγRIIB 小鼠皮肤和肺纤维化的严重程度明显高于 WT 小鼠。在博来霉素处理的小鼠皮肤中，FcγRIIB 小鼠的 CD8 T 细胞、F4/80 巨噬细胞、MPO 中性粒细胞、NK1.1NK 细胞和 B220 B 细胞数量明显高于 WT 小鼠。FcγRIIB 小鼠的 TNF-α 和 IL-1β 表达明显高于 WT 小鼠，受影响皮肤中 ICAM-1、CXCL2 和 CCL3 的表达也明显高于 WT 小鼠。与未进行过继转移的 WT 小鼠相比，将 FcγRIIB 小鼠的脾白细胞过继转移到 WT 小鼠中可导致皮肤和肺纤维化加重。