Regional disturbance of the distribution of T regulatory cells and T helper cells associated with irregular-shaped germinal centers in immunoglobulin G4-related sialadenitis
Regional disturbance of the distribution of T regulatory cells and T helper cells associated with irregular-shaped germinal centers in immunoglobulin G4-related sialadenitis
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DOI：
10.1007/s00428-021-03187-2
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发表时间：
2021-08
期刊：
影响因子：
3.5
通讯作者：
S. Kasashima;A. Kawashima;N. Kurose;S. Ozaki;H. Ikeda;K. Harada
中科院分区：
文献类型：
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作者：
S. Kasashima;A. Kawashima;N. Kurose;S. Ozaki;H. Ikeda;K. Harada
虽然已有许多生发中心（GCs）在免疫球蛋白（Ig） g4相关疾病中的报道，但GCs在igg4相关疾病中的意义尚未得到重视。T滤泡调节细胞（Tfr）是胃癌中的调节性T细胞（Treg）， T滤泡辅助细胞（Tfh）产生细胞因子白细胞介素(IL)-10并调节胃癌的发育。在手术标本的免疫组织化学全切片图像分析中，igg4相关的硬化性涎腺炎（IgG4-SS,n= 17）的特征是与对照组相比，涎腺总面积明显增加，IL-10 +细胞和Tfr和Tfh增加，包括慢性涎腺炎（n= 17）和Sjögren综合征（n= 15）患者。特别是IgG4-SS中GC中心区域的Tfr数量和Tfr/Tfh比值均高于对照组。中心区Tfr的数量与IgG4 +浆细胞的数量以及GCs的数量、大小和不规则性显著相关。在围绕GCs的地幔区域，IgG4-SS的Treg数量和Treg/T辅助细胞（Th）比高于对照组。在IgG4-SS中，Treg/Th比值在gc外的地幔区域最高，Tfr/Tfh比值在gc内的中心区域最高。而在对照组中，Treg/Th比值由外向内逐渐降低。我们的研究结果表明，GCs的形态异常以及GCs内外不同腔室中Treg和Th的特征性定位和平衡改变可能是IgG4-SS的新标志。
Although many germinal centers (GCs) have been reported in immunoglobulin (Ig) G4-related disease, the significance of GCs in IgG4-related disease has not received attention. Both T follicular regulatory cells (Tfr), which are regulatory T cells (Treg) in GCs, and T follicular helper cells (Tfh) produce the cytokine interleukin (IL)-10 and regulate GC development. In whole-slide image analysis in surgical specimens using immunohistochemistry, IgG4-related sclerosing sialadenitis (IgG4-SS,n= 17) was characterized by markedly numerous, large, and irregular-shaped GCs with increased IL-10 + cells and Tfr and Tfh in the total area of the salivary gland compared with controls, including patients with chronic sialadenitis (n= 17) and Sjögren syndrome (n= 15). In particular, the central area of GC in IgG4-SS showed a higher Tfr number and Tfr/Tfh ratio than controls. The number of Tfr in the central area was significantly correlated with the number of IgG4 + plasmacytes and the number, size, and irregularity of GCs. In the mantle area, which surrounds GCs, IgG4-SS showed a higher Treg number and Treg/T helper cells (Th) ratio than controls. In IgG4-SS, the Treg/Th ratio was highest in the mantle area outside GCs and the Tfr/Tfh ratio was highest in the central area inside GCs. However, in controls, the Treg/Th ratio gradually decreased from outside to inside GCs. Our findings reveal that the morphological abnormality of GCs and the characteristic localization and altered balance of Treg and Th in the different compartments of inside and outside GCs would be the novel hallmarks of IgG4-SS.