Interleukin-33 produced by M2 macrophages and other immune cells contributes to Th2 immune reaction of IgG4-related disease.
Interleukin-33 produced by M2 macrophages and other immune cells contributes to Th2 immune reaction of IgG4-related disease.
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DOI：
10.1038/srep42413
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发表时间：
2017-02-13
影响因子：
4.6
通讯作者：
Nakamura S
中科院分区：
文献类型：
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作者：
Furukawa S;Moriyama M;Miyake K;Nakashima H;Tanaka A;Maehara T;Iizuka-Koga M;Tsuboi H;Hayashida JN;Ishiguro N;Yamauchi M;Sumida T;Nakamura S
IgG 4相关疾病（IgG 4-RD）的特征是血清IgG 4升高和多个器官中IgG 4阳性细胞的显著浸润。白细胞介素-33（IL-33）是最近描述的由受损的上皮细胞、巨噬细胞和树突细胞分泌的细胞因子，并且有效地激活辅助性T 2型（Th 2）免疫应答，其已经被认为在IgG 4的IgG 4-RD产生中起主要作用。在这里，我们评估了IL-33和相关分子在IgG 4-RD患者唾液腺（SG）中的表达，与干燥综合征（SS）患者和对照组相比。IL-33及其受体（ST 2）在IgG 4-RD患者的SG中的异位生发中心（GC）周围强烈地检测到表达，而IL-33仅在SS患者和对照组的上皮细胞中表达。IgG 4-RD患者的IL-33和CD 68 +/CD 163+巨噬细胞主要分布于异位GC周围。免疫荧光双标显示IL-33与CD 68 +/CD 163+巨噬细胞共定位。最后，IL-33的mRNA表达水平与IgG 4-RD患者的Th 2细胞因子（IL-4和IL-13）的表达水平呈正相关。我们的数据表明，IL-33产生的M2巨噬细胞可能有助于通过异常激活的Th 2免疫反应的IgG 4-RD的发病机制。
IgG4-related disease (IgG4-RD) is characterized by elevated serum IgG4 and marked infiltration of IgG4-positive cells in multiple organs. Interleukin-33 (IL-33) is a recently described cytokine that is secreted by damaged epithelial cells, macrophages, and dendritic cells, and potently activates helper T type 2 (Th2) immune responses, which have been suggested to play a major role in IgG4 production of IgG4-RD. Here, we assessed the expression of IL-33 and related molecules in the salivary glands (SGs) of patients with IgG4-RD versus that in patients with Sjögren’s syndrome (SS) and controls. Expression of IL-33 and its receptor (ST2) was strongly detected around ectopic germinal centers (GCs) in the SGs from patients with IgG4-RD, whereas IL-33 was expressed only in epithelial cells in patients with SS and controls. Moreover, IL-33 and CD68+/CD163+ macrophages were mainly distributed around ectopic GCs in patients with IgG4-RD. Double immunofluorescence staining showed that IL-33 expression co-localized with CD68+/CD163+ macrophages. Finally, mRNA expression levels of IL-33 showed a positive correlation to those of Th2 cytokines (IL-4 and IL-13) in patients with IgG4-RD. Our data suggest that IL-33 produced by M2 macrophages might contribute to the pathogenesis of IgG4-RD via aberrant activation of Th2 immune responses.