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Expression and regulation of Siglec-6 (CD327) on human mast cells and basophils
Journal of Allergy and Clinical Immunology ( IF 14.2 ) Pub Date : 2022-08-08 , DOI: 10.1016/j.jaci.2022.07.018
Dubravka Smiljkovic 1 , Harald Herrmann 2 , Irina Sadovnik 1 , Susanne Gamperl 3 , Daniela Berger 3 , Gabriele Stefanzl 3 , Gregor Eisenwort 1 , Gregor Hoermann 4 , Sonja Kopanja 5 , Yulia Dorofeeva 6 , Margarete Focke-Tejkl 7 , Peter Jaksch 8 , Konrad Hoetzenecker 8 , Zsolt Szepfalusi 5 , Rudolf Valenta 7 , Michel Arock 9 , Peter Valent 1
Affiliation  

Background

Mast cells (MC) and basophils are effector cells of allergic reactions and display a number of activation-linked cell surface antigens. Of these antigens, however, only a few are functionally relevant and specifically expressed in these cells.

Objective

We sought to identify MC- and basophil-specific surface molecules and to study their cellular distribution and regulation during cytokine-induced and IgE-dependent activation.

Methods

Multicolor flow cytometry was performed to recognize surface antigens and to determine changes in antigen expression upon activation.

Results

We identified Siglec-6 (CD327) as a differentially regulated surface antigen on human MC and basophils. In the bone marrow, Siglec-6 was expressed abundantly on MC in patients with mastocytosis and in reactive states, but it was not detected on other myeloid cells, with the exception of basophils and monocytes. In healthy individuals, allergic patients, and patients with chronic myeloid leukemia (CML), Siglec-6 was identified on CD203c+ blood basophils, a subset of CD19+ B lymphocytes, and few CD14+ monocytes, but not on other blood leukocytes. CML basophils expressed higher levels of Siglec-6 than normal basophils. IL-3 promoted Siglec-6 expression on normal and CML basophils, and stem cell factor increased the expression of Siglec-6 on tissue MC. Unexpectedly, IgE-dependent activation resulted in downregulation of Siglec-6 in IL-3–primed basophils, whereas in MC, IgE-dependent activation augmented stem cell factor–induced upregulation of Siglec-6.

Conclusions

Siglec-6 is a dynamically regulated marker of MC and basophils. Activated MC and basophils exhibit unique Siglec-6 responses, including cytokine-dependent upregulation and unique, cell-specific, responses to IgE-receptor cross-linking.



中文翻译:

Siglec-6 (CD327) 在人肥大细胞和嗜碱性粒细胞上的表达和调控

背景

肥大细胞 (MC) 和嗜碱性粒细胞是过敏反应的效应细胞,并显示许多激活相关的细胞表面抗原。然而,在这些抗原中,只有少数具有功能相关性并在这些细胞中特异性表达。

客观的

我们试图确定 MC 和嗜碱性粒细胞特异性表面分子,并研究它们在细胞因子诱导和 IgE 依赖性激活过程中的细胞分布和调节。

方法

进行多色流式细胞术以识别表面抗原并确定激活后抗原表达的变化。

结果

我们将 Siglec-6 (CD327) 鉴定为人类 MC 和嗜碱性粒细胞上差异调节的表面抗原。在骨髓中,Siglec-6 在肥大细胞增多症和反应性状态患者的 MC 上大量表达,但在除嗜碱性粒细胞和单核细胞外的其他骨髓细胞上未检测到。在健康个体、过敏患者和慢性粒细胞白血病 (CML) 患者中,Siglec-6 在 CD203c +血嗜碱性粒细胞、CD19 + B 淋巴细胞亚群和少量 CD14 +单核细胞,而不是其他血液白细胞。CML 嗜碱性粒细胞比正常嗜碱性粒细胞表达更高水平的 Siglec-6。IL-3促进正常和CML嗜碱性粒细胞上Siglec-6的表达,干细胞因子增加Siglec-6在组织MC上的表达。出乎意料的是,IgE 依赖性激活导致 IL-3 引发的嗜碱性粒细胞中 Siglec-6 下调,而在 MC 中,IgE 依赖性激活增强了干细胞因子诱导的 Siglec-6 上调。

结论

Siglec-6 是 MC 和嗜碱性粒细胞的动态调节标记。活化的 MC 和嗜碱性粒细胞表现出独特的 Siglec-6 反应,包括细胞因子依赖性上调和独特的细胞特异性对 IgE 受体交联的反应。

更新日期:2022-08-08
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