CXC趋化因子受体3对神经系统疾病发生发展影响的研究进展

doi:10.13481/j.1671-587X.20240535

Abstract

Abstract:

Chemokines and their receptors play crucial roles in nervous system diseases， among which the CXC chemokine receptor 3 （CXCR3） is an important mediator of intercellular communication. CXCR3 not only participates in inflammatory chemotaxis and malignant behaviors of tumor cells but also regulates the neurologic diseases. CXCR3 and its ligands directly or indirectly contribute to neuroinflammation and neuroimmunity， and potentially serve as therapeutic targets for diseases like multiple sclerosis， Alzheimer’s disease， and glioma and so on. This review discusses the expression and impact of CXCR3 and its ligands in neurological diseases such as multiple sclerosis， neurologic tumors， neurodegenerative diseases， and neuropathic pain， as well as their associations with CXCR3 ligands. Understanding the mechanisms linking CXCR3 to these diseases could facilitate its potential as an early diagnostic biomarker and a target for drug intervention， and provide the basis of studying the occurrence and developmant of nervous system disease.

Key words: Chemokine receptor 3, CXC chemokine receptor 3 ligands, Neurological inflammation, Neurological tumor, Neurodegenerative diseases

CLC Number:

R741.02

Wenhui LIU,Miao YU,Ying GUO,Yupeng LIU,Yang XING,Xinyu HONG,Jiale CUI. Research progress in effect of CXC chemokine receptor 3 on occurrence and development of nervous system diseases[J].Journal of Jilin University(Medicine Edition), 2024, 50(5): 1474-1480.

References 53

1	MOSER B， LOETSCHER P. Lymphocyte traffic control by chemokines［J］. Nat Immunol， 2001， 2（2）： 123-128.
2	BENDALL L. Chemokines and their receptors in disease［J］. Histol Histopathol， 2005， 20（3）： 907-926.
3	SORCE S， MYBURGH R， KRAUSE K H. The chemokine receptor CCR5 in the central nervous system［J］. Prog Neurobiol， 2011， 93（2）： 297-311.
4	TAKACS G P， FLORES-TORO J A， HARRISON J K. Modulation of the chemokine/chemokine receptor axis as a novel approach for glioma therapy［J］. Pharmacol Ther， 2021， 222： 107790.
5	XIA M Q， BACSKAI B J， KNOWLES R B， et al. Expression of the chemokine receptor CXCR3 on neurons and the elevated expression of its ligand IP-10 in reactive astrocytes： in vitro ERK1/2 activation and role in Alzheimer’s disease［J］. J Neuroimmunol， 2000， 108（1/2）： 227-235.
6	ZLOTNIK A， YOSHIE O. Chemokines： a new classification system and their role in immunity［J］. Immunity， 2000， 12（2）： 121-127.
7	MANTOVANI A. The chemokine system： redundancy for robust outputs［J］. Immunol Today， 1999， 20（6）： 254-257.
8	LU C， ZHU J， CHEN X J， et al. Risk stratification in acute myeloid leukemia using CXCR gene signatures： a bioinformatics analysis［J］. Front Oncol， 2020， 10： 584766.
9	STONE M J， HAYWARD J A， HUANG C， et al. Mechanisms of regulation of the chemokine-receptor network［J］. Int J Mol Sci， 2017， 18（2）： 342.
10	ALTARA R， MANCA M， BRANDÃO R D， et al. Emerging importance of chemokine receptor CXCR3 and its ligands in cardiovascular diseases［J］. Clin Sci， 2016， 130（7）： 463-478.
11	CAO F， CHEN S S， YAN X F， et al. Evaluation of side effects through selective ablation of the mu opioid receptor expressing descending nociceptive facilitatory neurons in the rostral ventromedial medulla with dermorphin-saporin［J］. Neurotoxicology， 2009， 30（6）： 1096-1106.
12	赵家华，岑雨樱，许晓娇，等. 1247例中枢神经系统感染性疾病的流行病学及临床特征：一项单中心回顾性分析［J. 解放军医学杂志， 2024， 49（1）： 43-49.
13	CANNON A， THOMPSON C M， BHATIA R， et al. Contribution of CXCR3-mediated signaling in the metastatic cascade of solid malignancies［J］. Biochim Biophys Acta Rev Cancer， 2021， 1876（2）： 188628.
14	李佳，吴珺，杨东亮. CXCR3-CXCL9/10/11参与疾病发病机制的研究进展［J］. 中国免疫学杂志， 2020， 36（10）： 1266-1270.
15	BANISADR G， ROSTÈNE W， KITABGI P， et al. Chemokines and brain functions［J］. Curr Drug Targets Inflamm Allergy， 2005， 4（3）： 387-399.
16	MÜLLER M， CARTER S， HOFER M J， et al. Review： the chemokine receptor CXCR3 and its ligands CXCL9， CXCL10 and CXCL11 in neuroimmunity： a tale of conflict and conundrum［J］. Neuropathol Appl Neurobiol， 2010， 36（5）： 368-387.
17	RAMESH G， MACLEAN A G， PHILIPP M T. Cytokines and chemokines at the crossroads of neuroinflammation， neurodegeneration， and neuropathic pain［J］. Mediators Inflamm， 2013， 2013： 480739.
18	SATARKAR D， PATRA C. Evolution expression and functional analysis of CXCR3 in neuronal and cardiovascular diseases： a narrative review［J］. Front Cell Dev Biol， 2022， 10： 882017.
19	PIOTROWSKA A， ROJEWSKA E， PAWLIK K， et al. Pharmacological blockade of CXCR3 by （±）-NBI-74330 reduces neuropathic pain and enhances opioid effectiveness-Evidence from in vivo and in vitro studies［J］. Biochim Biophys Acta Mol Basis Dis， 2018， 1864（10）： 3418-3437.
20	OWENS T， BABCOCK A A， MILLWARD J M， et al. Cytokine and chemokine inter-regulation in the inflamed or injured CNS［J］. Brain Res Brain Res Rev， 2005， 48（2）： 178-184.
21	BALASHOV K E， ROTTMAN J B， WEINER H L， et al. CCR5（+） and CXCR3（+） T cells are increased in multiple sclerosis and their ligands MIP-1alpha and IP-10 are expressed in demyelinating brain lesions［J］. Proc Natl Acad Sci USA， 1999， 96（12）： 6873-6878.
22	FIFE B T， KENNEDY K J， PANIAGUA M C， et al. CXCL10 （IFN-gamma-inducible protein-10） control of encephalitogenic CD4+ T cell accumulation in the central nervous system during experimental autoimmune encephalomyelitis［J］. J Immunol， 2001， 166（12）： 7617-7624.
23	SØRENSEN T L， TREBST C， KIVISÄKK P， et al. Multiple sclerosis： a study of CXCL10 and CXCR3 co-localization in the inflamed central nervous system［J］. J Neuroimmunol， 2002， 127（1/2）： 59-68.
24	KOCH-HENRIKSEN N， SØRENSEN P S. The changing demographic pattern of multiple sclerosis epidemiology［J］. Lancet Neurol， 2010， 9（5）： 520-532.
25	KAUR G， TROWSDALE J， FUGGER L. Natural killer cells and their receptors in multiple sclerosis［J］. Brain， 2013， 136（Pt 9）： 2657-2676.
26	CICCARELLI O， BARKHOF F， BODINI B， et al. Pathogenesis of multiple sclerosis： insights from molecular and metabolic imaging［J］. Lancet Neurol， 2014， 13（8）： 807-822.
27	SØRENSEN T L， TANI M， JENSEN J， et al. Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients［J］. J Clin Invest， 1999， 103（6）： 807-815.
28	LI J， SHI J Y， SUN Y， et al. Glycyrrhizin， a potential drug for autoimmune encephalomyelitis by inhibiting high-mobility group box 1［J］. DNA Cell Biol， 2018， 37（12）： 941-946.
29	OMARI K M， JOHN G R， SEALFON S C， et al. CXC chemokine receptors on human oligodendrocytes： implications for multiple sclerosis［J］. Brain， 2005， 128（Pt 5）： 1003-1015.
30	KOHLER R E， COMERFORD I， TOWNLEY S， et al. Antagonism of the chemokine receptors CXCR3 and CXCR4 reduces the pathology of experimental autoimmune encephalomyelitis［J］. Brain Pathol， 2008， 18（4）： 504-516.
31	LIU L P， HUANG D R， MATSUI M， et al. Severe disease， unaltered leukocyte migration， and reduced IFN-gamma production in CXCR3^-/- mice with experimental autoimmune encephalomyelitis［J］. J Immunol， 2006， 176（7）： 4399-4409.
32	MÜLLER M， CARTER S L， HOFER M J， et al. CXCR3 signaling reduces the severity of experimental autoimmune encephalomyelitis by controlling the parenchymal distribution of effector and regulatory T cells in the central nervous system［J］. J Immunol， 2007， 179（5）： 2774-2786.
33	MA B， KHAZALI A， WELLS A. CXCR3 in carcinoma progression［J］. Histol Histopathol， 2015， 30（7）： 781-792.
34	WENNERBERG E， KREMER V， CHILDS R， et al. CXCL10-induced migration of adoptively transferred human natural killer cells toward solid tumors causes regression of tumor growth in vivo ［J］. Cancer Immunol Immunother， 2015， 64（2）： 225-235.
35	LI J， YBARRA R， MAK J， et al. IFNγ-induced chemokines are required for CXCR3-mediated T-cell recruitment and antitumor efficacy of anti-HER2/CD3 bispecific antibody［J］. Clin Cancer Res， 2018， 24（24）： 6447-6458.
36	冯珺，吴昌平，蒋敬庭. CXCR3及其配体在肿瘤中的研究进展［J］. 临床检验杂志， 2019， 37（2）： 129-132.
37	冯海忠. 组蛋白修饰与胶质瘤发生发展［J］. 上海交通大学学报（医学版）， 2018， 38（1）： 1-3.
38	DOLECEK T A， PROPP J M， STROUP N E， et al. CBTRUS statistical report： primary brain and central nervous system tumors diagnosed in the United States in 2005-2009［J］. Neuro Oncol， 2012， 14（）： v1-v49.
39	PU Y， LI S W， ZHANG C B， et al. High expression of CXCR3 is an independent prognostic factor in glioblastoma patients that promotes an invasive phenotype［J］. J Neurooncol， 2015， 122（1）： 43-51.
40	SHONO K， YAMAGUCHI I， MIZOBUCHI Y， et al. Downregulation of the CCL2/CCR2 and CXCL10/CXCR3 axes contributes to antitumor effects in a mouse model of malignant glioma［J］. Sci Rep， 2020， 10（1）： 15286.
41	LIU C， LUO D F， REYNOLDS B A， et al. Chemokine receptor CXCR3 promotes growth of glioma［J］. Carcinogenesis， 2011， 32（2）： 129-137.
42	ROMAGNANI P， LASAGNI L， ANNUNZIATO F， et al. CXC chemokines： the regulatory link between inflammation and angiogenesis［J］. Trends Immunol， 2004， 25（4）： 201-209.
43	舒凯，雷霆，朱洪涛，等. 脑胶质瘤免疫治疗进展与展望［J］. 临床外科杂志， 2022， 30（10）： 917-919.
44	LIU C， CUI G H， ZHU M P， et al. Neuroinflammation in Alzheimer’s disease： chemokines produced by astrocytes and chemokine receptors［J］. Int J Clin Exp Pathol， 2014， 7（12）： 8342-8355.
45	HEEMELS M T. Neurodegenerative diseases［J］. Nature， 2016， 539（7628）： 179.
46	李立琳，胡敬龙，徐运，等. 小胶质细胞中的脂滴在中枢神经系统疾病中的研究进展［J］. 中风与神经疾病杂志， 2024， 41（7）： 655-660.
47	KRAUTHAUSEN M， KUMMER M P， ZIMMERMANN J， et al. CXCR3 promotes plaque formation and behavioral deficits in an Alzheimer’s disease model［J］. J Clin Invest， 2015， 125（1）： 365-378.
48	GILRON I， BARON R， JENSEN T. Neuropathic pain： principles of diagnosis and treatment［J］. Mayo Clin Proc， 2015， 90（4）： 532-545.
49	CHEN Y L， YIN D K， FAN B B， et al. Chemokine CXCL10/CXCR3 signaling contributes to neuropathic pain in spinal cord and dorsal root Ganglia after chronic constriction injury in rats［J］. Neurosci Lett， 2019， 694： 20-28.
50	JIANG B C， HE L N， WU X B， et al. Promoted interaction of C/EBPα with demethylated CXCR3 gene promoter contributes to neuropathic pain in mice［J］. J Neurosci， 2017， 37（3）： 685-700.
51	WU S F， WANG Y， ZHAO Q C. Demethylase FTO promotes neuropathic pain development via regulating the m6A methylation levels of CXCR3［J］. Acta Biochim Pol， 2022， 69（4）： 819-824.
52	KONG Y F， SHA W L， WU X B， et al. CXCL10/CXCR3 signaling in the DRG exacerbates neuropathic pain in mice［J］. Neurosci Bull， 2021， 37（3）： 339-352.
53	伍湘平，张露，黄行行，等. 基于FAERS数据库的羟考酮中枢神经系统不良事件信号挖掘及分析［J］. 中南大学学报（医学版）， 2023， 48（3）： 422-434.

[1]	Sifan FENG,Yunfeng LI,Jiaying WANG,Fubin MA,Yan WANG. Effects of heme-binding protein 1 gene knockdown on proliferation, migration, and inflammatory response of microglia BV2 and their mechanisms [J]. Journal of Jilin University(Medicine Edition), 2025, 51(6): 1532-1541.
[2]	Xiaohua LIU,Bingying FANG,Man HAN,Haifa QIAO,Yuanwang YU. Analgesic effect of baicalein on neuropathic pain of rats and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2022, 48(3): 600-605.
[3]	Haqi LI,Chensi SUN,Haibei LIU,Kaili CHEN,Lei XU,Jinting HE. Opalski syndrome:A report of 5 cases and literature review [J]. Journal of Jilin University(Medicine Edition), 2021, 47(6): 1544-1549.
[4]	YANG Dong-Wei, SONG Xue-Song, WANG Peng, WANG Chun-Xi. Effects of intrathecal injection of NOS inhibitors on \|phosphorylated CREB expression in spinal cord of CCD-induced neuropathic pain rats [J]. J4, 2009, 35(6): 1020-1023.
[5]	WU Hui, FANG Yan-qiu，WANG Dong-xuan, TAN Yan. Effects of topiramate on hydrous capacity in brain tissue and neurons apoptosis in rats with perinatal ischemic brain damage [J]. J4, 2006, 32(6): 1041-1044.

Research progress in effect of CXC chemokine receptor 3 on occurrence and development of nervous system diseases

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

References 53

Related Articles 5

Metrics

Comments

Recommended 10