Ⅰ型固有淋巴细胞及相关细胞因子在原发免疫性血小板减少症中的变化及临床意义

doi:10.11958/20251351

天津医药 ›› 2025, Vol. 53 ›› Issue (8): 791-795.doi: 10.11958/20251351

Ⅰ型固有淋巴细胞及相关细胞因子在原发免疫性血小板减少症中的变化及临床意义

王秀娟(), 布阿斯亚木·喀迪尔江, 王洪波, 洪佳乐, 孙明玲, 郭新红^△()

新疆医科大学第一附属医院血液病中心，新疆维吾尔自治区血液病研究所（邮编830000）

收稿日期:2025-04-01 修回日期:2025-05-27 出版日期:2025-08-15 发布日期:2025-08-12
通讯作者: ^△E-mail：guoxinhong222@sina.cn
作者简介:王秀娟（1986），女，主治医师，主要从事止血与血栓性疾病方面研究。E-mail：196469066@qq.com
基金资助:
新疆维吾尔自治区自然科学基金青年项目(2021D01C333)

Changes and clinical significance of type I innate lymphoid cells and associated cytokines in primary immune thrombocytopenia

WANG Xiujuan(), KADIERJIANG Buasiyamu, WANG Hongbo, HONG Jiale, SUN Mingling, GUO Xinhong^△()

Blood Disease Center of the First Affiliated Hospital of Xinjiang Medical University, Hematology Institute of Xinjiang Uygur Autonomous Region, Urumqi 830000, China

Received:2025-04-01 Revised:2025-05-27 Published:2025-08-15 Online:2025-08-12
Contact: ^△E-mail：guoxinhong222@sina.cn

王秀娟, 布阿斯亚木·喀迪尔江, 王洪波, 洪佳乐, 孙明玲, 郭新红. Ⅰ型固有淋巴细胞及相关细胞因子在原发免疫性血小板减少症中的变化及临床意义[J]. 天津医药, 2025, 53(8): 791-795.

WANG Xiujuan, KADIERJIANG Buasiyamu, WANG Hongbo, HONG Jiale, SUN Mingling, GUO Xinhong. Changes and clinical significance of type I innate lymphoid cells and associated cytokines in primary immune thrombocytopenia[J]. Tianjin Medical Journal, 2025, 53(8): 791-795.

摘要/Abstract

摘要：

目的探讨原发免疫性血小板减少症（ITP）患者外周血中Ⅰ型固有淋巴细胞（ILC1s）、T盒子转录因子（T-bet）及白细胞介素（IL）-12、IL-18和干扰素γ（IFN-γ）的表达水平及临床意义。方法选取首次发病的35例ITP患者作为初治组，其中13例在治疗后接受随访，另选取同期20例健康体检者为对照组。采集外周血，使用流式细胞术检测ILC1s比例，实时荧光定量PCR（qRT-PCR）检测T-bet mRNA表达水平，酶联免疫吸附试验（ELISA）检测血清IL-18、IL-12和IFN-γ水平；比较各组间ILC1s、T-bet mRNA、IL-18、IL-12和IFN-γ的差异，分析ILC1s比例与T-bet mRNA、IL-18、IL-12、IFN-γ水平和血小板（PLT）计数相关性。结果初治组ILC1s比例，T-bet mRNA表达水平，血清IL-12、IL-18和IFN-γ水平均高于对照组（P<0.05）。13例ITP患者治疗后上述指标均较治疗前明显下降（P<0.05）。相关性分析显示初治组ILC1s细胞比例与IL-12、IL-18、IFN-γ和T-bet mRNA水平呈正相关（r_s分别为0.666、0.647、0.677和0.750，均P<0.01），与PLT计数呈负相关（r_s=-0.637，P<0.01）。结论固有免疫可能通过调控ILC1s、T-bet及IL-12、IL-18、IFN-γ参与ITP的发病及转归。

关键词: 血小板减少, 淋巴细胞, T盒域蛋白质类, 白细胞介素12, 白细胞介素18, 干扰素γ, 原发免疫性血小板减少症, Ⅰ型固有淋巴细胞

Abstract:

Objective To investigate the expression levels and clinical significance of type Ⅰ innate lymphoid cells (ILC1s), T-box transcription factor (T-bet), interleukin (IL)-12, IL-18 and interferon-gamma (IFN-γ) in peripheral blood of patients with primary immune thrombocytopenia (ITP). Methods Thirty-five ITP patients with their first episode were selected as the initial treatment group. Thirteen of these patients were followed up after receiving treatment. Additionally, 20 healthy individuals underwent routine physical examinations during the same period were recruited as the control group. Peripheral blood samples were collected for analysis. The proportion of ILC1s was determined by flow cytometry. T-bet mRNA expression was measured using quantitative real-time PCR (qRT-PCR). Serum levels of IL-18, IL-12 and IFN-γ were quantified by enzyme-linked immunosorbent assay (ELISA). The differences in ILC1s proportion, T-bet mRNA expression and cytokine levels were compared between groups. Correlations between ILC1s proportion, T-bet mRNA, cytokine levels and platelet (PLT) counts were also analyzed. Results Compared with the control group, the initial treatment group exhibited significantly elevated levels of peripheral ILC1s, T-bet mRNA and serum IL-18, IL-12 and IFN-γ (P<0.05). Among the 13 patients who were followed up, all these indices decreased significantly after treatment (P<0.05). Correlation analysis revealed that the proportion of ILC1s in the initial treatment group was positively correlated with IL-12, IL-18, IFN-γ and T-bet mRNA levels (r_s = 0.666, 0.647, 0.677, and 0.750, respectively, P<0.01), and negatively correlated with PLT count (r_s= -0.637, P<0.01). Conclusion Innate immunity may play a role in the pathogenesis and progression of ITP by regulating the expression levels of ILC1s, T-bet, IL-12, IL-18 and IFN-γ.

Key words: thrombocytopenia, lymphocytes, T-box domain proteins, interleukin-12, interleukin-18, interferon-gamma, primary immune thrombocytopenia, type Ⅰ innate lymphoid cells

中图分类号:

R558.2

图/表 4

图1 ILC1s流式圈门图 A：通过前向散射（FSC）和侧向散射（SSC）圈出淋巴细胞；B：通过前向散射面积（FSC-A）和前向散射高度（FSC-H）去除粘连细胞；C：通过SSC和CD45圈出CD45+细胞群；D：以Lineage-和CD127+设门圈出总固有淋巴细胞群；E：以CD294-和CD117-设门圈出ILC1s。

Fig.1 Flow cytometry gating strategy for ILC1s

表1 2组外周血中ILC1s、T-bet mRNA、IL-18、IL-12和IFN-γ比较

Tab.1 Comparison of ILC1s, T-bet mRNA, IL-18, IL-12 and IFN-γ levels in peripheral blood between the two groups

组别	n	ILC1s/%	T-bet mRNA
对照组	20	23.76（18.72,29.82）	0.85（0.34,1.55）
初治组	35	40.11（28.21,42.74）	1.83（1.28,4.91）
Z		4.086^＊＊	3.692^＊＊
组别	IL-18/（ng/L）	IL-12/（ng/L）	IFN-γ/（ng/L）
对照组	46.45±11.91	1.15±0.33	205.57±40.39
初治组	77.15±25.55	2.14±0.59	400.22±65.46
t	6.048^＊＊	7.862^＊＊	13.628^＊＊

表2 ITP患者治疗前后ILC1s、T-bet mRNA、IL-18、IL-12和IFN-γ比较

Tab.2 Comparison of ILC1s, T-bet mRNA, IL-18, IL-12 and IFN-γ levels in ITP patients before and after treatment between the two groups （n=13）

时期		ILC1s/%	T-bet mRNA
治疗前		39.13（32.40,42.30）	2.34（1.14，4.27）
治疗后		19.23（15.93，30.99）	0.72（0.51，1.02）
Z		3.180^＊＊	2.900^＊＊
时期	IL-18/（ng/L）	IL-12/（ng/L）	IFN-γ/（ng/L）
治疗前	80.10（71.59,104.63）	2.55（1.96,3.07）	342.92（314.81,382.09）
治疗后	54.42（36.47,65.50）	1.50（1.33,1.50)	233.05（193.86,264.13）
Z	3.110^＊＊	3.180^＊＊	2.970^＊＊

图2 ILC1s与IL-12、IL-18、IFN-γ、T-bet mRNA和PLT计数的相关性

Fig.2 Correlation of ILC1s with IL-12, IL-18, IFN-γ, T-bet mRNA and PLT

参考文献 19

[1]	HE X, LI N, LIU D, et al. Regulatory role of ceRNA network in B lymphocytes of patients with immune thrombocytopenia[J]. Autoimmunity, 2023, 56(1):2281225. doi:10.1080/08916934.2023.2281225.
[2]	LIU S Y, QU H T, SUN R J, et al. High-throughput DNA methylation analysis in ITP confirms NOTCH1 hypermethylation through the Th1 and Th2 cell differentiation pathways[J]. Int Immunopharmacol, 2022,111:109105. doi:10.1016/j.intimp.2022.109105.
[3]	王秀娟, 孙明玲, 刘颖, 等. sST2/IL-33与Th17/Treg相关细胞因子在原发免疫性血小板减少症中的作用研究[J]. 天津医药, 2019, 47(7):732-734.
	WANG X J, SUN M L, LIU Y, et al. Study of sST2/IL-33 and Th17/Treg related cytokines on patients with primary immune thrombocytopenia[J]. Tianjin Med J, 2019, 47(7):732-734. doi:10.11958/20182195.
[4]	WANG X, ZHOU Q, YANG W, et al. The role of CD83 in the pathogenesis of immune thrombocytopenia[J]. Hematology, 2024, 29(1):2372482. doi:10.1080/16078454.2024.2372482.
[5]	CAO J, JI L, ZHAN Y, et al. MST4 kinase regulates immune thrombocytopenia by phosphorylating STAT1-mediated M1 polarization of macrophages[J]. Cell Mol Immunol, 2023, 20(12):1413-1427. doi:10.1038/s41423-023-01089-8.
[6]	SRIVASTAVA R K, SAPRA L, BHARDWAJ A, et al. Unravelling the immunobiology of innate lymphoid cells (ILCs):implications in health and disease[J]. Cytokine Growth Factor Rev, 2023, 74:56-75. doi:10.1016/j.cytogfr.2023.09.002.
[7]	KORCHAGINA A A, SHEIN S A, KOROLEVA E, et al. Transcriptional control of ILC identity[J]. Front Immunol, 2023,14:1146077. doi:10.3389/fimmu.2023.1146077.
[8]	CLOTTU A S, HUMBEL M, FLUDER N, et al. Innate lymphoid cells in autoimmune diseases[J]. Front Immunol, 2021,12:789788. doi:10.3389/fimmu.2021.789788.
[9]	KAWKA L, FELTEN R, SCHLEISS C, et al. Alteration of innate lymphoid cell homeostasis mainly concerns salivary glands in primary Sjögren's syndrome[J]. RMD Open, 2023, 9(2):e003051. doi:10.1136/rmdopen-2023-003051.
[10]	YANG F, LUO X, ZHU W, et al. Dysregulation of innate lymphoid cells in patients with active rheumatoid arthritis and mice with collagen-induced arthritis[J]. Mediators Inflamm, 2021,2021:1915068. doi:10.1155/2021/1915068.
[11]	AUDIA S, MOULINET T, CIUDAD-BONTÉ M, et al. Altered distribution and function of splenic innate lymphoid cells in adult chronic immune thrombocytopenia[J]. J Autoimmun, 2018, 93:139-144. doi:10.1016/j.jaut.2018.07.015.
[12]	WANG S C, YANG K D, LIN C Y, et al. Intravenous immunoglobulin therapy enhances suppressive regulatory T cells and decreases innate lymphoid cells in children with immune thrombocytopenia[J]. Pediatr Blood Cancer, 2020, 67(2):e28075. doi:10.1002/pbc.28075.
[13]	ZHONG L, WANG Y H, KAHLFUSS S, et al. STIM1-mediated NFAT signaling synergizes with STAT1 to control T-bet expression and TH1 differentiation[J]. Nat Immunol, 2025, 26(3):484-496. doi:10.1038/s41590-025-02089-8.
[14]	LIAO Z, YANG X, HE L, et al. Cordyceps protein alleviates renal injury by inhibiting T cell infiltration and Th1 cell differentiation in lupus nephritis mice[J]. Int Immunopharmacol, 2024,138:112566. doi:10.1016/j.intimp.2024.112566.
[15]	KANG J, LIGGETT J R, PATIL D, et al. Type 1 innate lymphoid cells are proinflammatory effector cells in ischemia-reperfusion injury of steatotic livers[J]. Front Immunol, 2022,13:899525. doi:10.3389/fimmu.2022.899525.
[16]	KRZYWINSKA E, SOBECKI M, NAGARAJAN S, et al. The transcription factor HIF-1α mediates plasticity of NKp46+ innate lymphoid cells in the gut[J]. J Exp Med, 2022, 219(2):e20210909. doi:10.1084/jem.20210909.
[17]	LI Q, YANG M, XIA R, et al. Elevated expression of IL-12 and IL-23 in patients with primary immune thrombocytopenia[J]. Platelets, 2015, 26(5):453-458. doi:10.3109/09537104.2014.934217.
[18]	LIU L, XU H, WANG J, et al. Trimethylamine-N-oxide (TMAO) and basic fibroblast growth factor(bFGF)are possibly involved in corticosteroid resistance in adult patients with immune thrombocytopenia[J]. Thromb Res, 2024, 233:25-36. doi:10.1016/j.thromres.2023.11.003.
[19]	WANG Z M, ZHANG J, WANG F, et al. The tipped balance of ILC1/ILC2 in peripheral blood of oral lichen planus is related to inflammatory cytokines[J]. Front Cell Dev Biol, 2021,9:725169. doi:10.3389/fcell.2021.725169.

Ⅰ型固有淋巴细胞及相关细胞因子在原发免疫性血小板减少症中的变化及临床意义

Changes and clinical significance of type I innate lymphoid cells and associated cytokines in primary immune thrombocytopenia

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