Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Research Article

Proteomic Analysis by 4D Label-free MS-PRM Provides Insight into the Role and Regulatory Mechanisms of IL-25 in NK Cells

Author(s): Juan Feng*, Luoyao Huang, Shuaipeng Yang, Jiasheng Pan, Xiangxing Zhu and Dongsheng Tang

Volume 30, Issue 10, 2023

Published on: 04 October, 2023

Page: [841 - 853] Pages: 13

DOI: 10.2174/0929866530666230911164329

Price: $65

Abstract

Background: NK cells play an important role in immune response, immune surveillance, and metabolism regulation. Therefore, NK cells are involved in the occurrence and development of various diseases, such as infectious diseases, cancer, obesity, and diabetes. IL-25 is a special member of the IL-17 family with anti-inflammatory function. IL-25 can regulate inflammatory response and metabolism via various immune cells; however, the role and regulatory mechanism of IL-25 in NK cells are still unclear.

Method: In this study, we investigate the role of IL-25 in NK-cell protein profile via 4D label-free mass spectrum and validate the differential proteins via PRM analysis. In addition, GO analysis, KEGG analysis, and other bioinformatic analysis methods are used to explore the enriched function and signal pathway of differentially expressed proteins.

Result and Discussion: The GO and KEGG analyses suggest that IL-25 may affect the processes, such as metabolism, thermogenesis, and oxidative phosphorylation of NK cells. There are 7 down-regulated proteins (NCR1, GZMB, PRF1, KLRC1, NDUFA11, LAMTOR5, and IKBIP) and 1 up-regulated protein (PSMD7) in IL-25-treated NK cells versus the control group for PRM validation. Our results indicate that IL-25 may regulate metabolism and other biological processes via NK cells, which will be beneficial in revealing the role and regulatory mechanisms of IL-25 in NK cells in various diseases.

Conclusion: Proteomics combined with bioinformatic analysis will help to mine more information hidden behind mass spectrometry data and lay the foundation for finding clinical biomarkers and mechanisms of diseases.

Keywords: Proteomics, mass spectrum, PRM, IL-25, NK cells, oxidative phosphorylation, anti-inflammatory, thermogenesis.

Graphical Abstract
[1]
Iwakura, Y.; Ishigame, H.; Saijo, S.; Nakae, S. Functional specialization of interleukin-17 family members. Immunity, 2011, 34(2), 149-162.
[http://dx.doi.org/10.1016/j.immuni.2011.02.012] [PMID: 21349428]
[2]
Owyang, A.M.; Zaph, C.; Wilson, E.H.; Guild, K.J.; McClanahan, T.; Miller, H.R.P.; Cua, D.J.; Goldschmidt, M.; Hunter, C.A.; Kastelein, R.A.; Artis, D. Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract. J. Exp. Med., 2006, 203(4), 843-849.
[http://dx.doi.org/10.1084/jem.20051496] [PMID: 16606667]
[3]
Shin, H.W.; Kim, D.K.; Park, M.H.; Eun, K.M.; Lee, M.; So, D.; Kong, I.G.; Mo, J.H.; Yang, M.S.; Jin, H.R.; Park, J.W.; Kim, D.W. IL-25 as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis. J. Allergy Clin. Immunol., 2015, 135(6), 1476-1485.e7.
[http://dx.doi.org/10.1016/j.jaci.2015.01.003] [PMID: 25725991]
[4]
Lee, M.; Kim, D.W.; Shin, H.W. Targeting IL-25 as a novel therapy in chronic rhinosinusitis with nasal polyps. Curr. Opin. Allergy Clin. Immunol., 2017, 17(1), 17-22.
[http://dx.doi.org/10.1097/ACI.0000000000000332] [PMID: 27870664]
[5]
Tamachi, T.; Maezawa, Y.; Ikeda, K.; Kagami, S.; Hatano, M.; Seto, Y.; Suto, A.; Suzuki, K.; Watanabe, N.; Saito, Y.; Tokuhisa, T.; Iwamoto, I.; Nakajima, H. IL-25 enhances allergic airway inflammation by amplifying a TH2 cell–dependent pathway in mice. J. Allergy Clin. Immunol., 2006, 118(3), 606-614.
[http://dx.doi.org/10.1016/j.jaci.2006.04.051] [PMID: 16950278]
[6]
Beale, J.; Jayaraman, A.; Jackson, D.J.; Macintyre, J.D.R.; Edwards, M.R.; Walton, R.P.; Zhu, J.; Ching, Y.M.; Shamji, B.; Edwards, M.; Westwick, J.; Cousins, D.J.; Hwang, Y.Y.; McKenzie, A.; Johnston, S.L.; Bartlett, N.W. Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation. Sci. Transl. Med., 2014, 6(256), 256ra134.
[http://dx.doi.org/10.1126/scitranslmed.3009124] [PMID: 25273095]
[7]
McGeachy, M.J.; Cua, D.J.; Gaffen, S.L. The IL-17 family of cytokines in health and disease. Immunity, 2019, 50(4), 892-906.
[http://dx.doi.org/10.1016/j.immuni.2019.03.021] [PMID: 30995505]
[8]
Chalubinski, M.; Luczak, E.; Wojdan, K.; Gorzelak-Pabis, P.; Broncel, M. Innate lymphoid cells type 2 – emerging immune regulators of obesity and atherosclerosis. Immunol. Lett., 2016, 179, 43-46.
[http://dx.doi.org/10.1016/j.imlet.2016.09.007] [PMID: 27646628]
[9]
Feng, J.; Li, L.; Ou, Z.; Li, Q.; Gong, B.; Zhao, Z.; Qi, W.; Zhou, T.; Zhong, J.; Cai, W.; Yang, X.; Zhao, A.; Gao, G.; Yang, Z. IL-25 stimulates M2 macrophage polarization and thereby promotes mitochondrial respiratory capacity and lipolysis in adipose tissues against obesity. Cell. Mol. Immunol., 2018, 15(5), 493-505.
[http://dx.doi.org/10.1038/cmi.2016.71] [PMID: 28194019]
[10]
Li, L.; Ma, L.; Zhao, Z.; Luo, S.; Gong, B.; Li, J.; Feng, J.; Zhang, H.; Qi, W.; Zhou, T.; Yang, X.; Gao, G.; Yang, Z. IL-25–induced shifts in macrophage polarization promote development of beige fat and improve metabolic homeostasis in mice. PLoS Biol., 2021, 19(8), e3001348.
[http://dx.doi.org/10.1371/journal.pbio.3001348] [PMID: 34351905]
[11]
Wang, A.J.; Yang, Z.; Grinchuk, V.; Smith, A.; Qin, B.; Lu, N.; Wang, D.; Wang, H.; Ramalingam, T.R.; Wynn, T.A.; Urban, J.F., Jr; Shea-Donohue, T.; Zhao, A. IL-25 or IL-17E protects against high-fat diet–induced hepatic steatosis in mice dependent upon IL-13 activation of STAT6. J. Immunol., 2015, 195(10), 4771-4780.
[http://dx.doi.org/10.4049/jimmunol.1500337] [PMID: 26423151]
[12]
Zheng, X.L.; Wu, J.P.; Gong, Y.; Hong, J.B.; Xiao, H.Y.; Zhong, J.W.; Xie, B.; Li, B.M.; Guo, G.H.; Zhu, X.; Wang, A.J. IL-25 protects against high-fat diet-induced hepatic steatosis in mice by inducing IL-25 and M2a macrophage production. Immunol. Cell Biol., 2019, 97(2), 165-177.
[http://dx.doi.org/10.1111/imcb.12207] [PMID: 30242904]
[13]
Bryceson, Y.T.; Fauriat, C.; Nunes, J.M.; Wood, S.M.; Björkström, N.K.; Long, E.O.; Ljunggren, H.G. Functional analysis of human NK cells by flow cytometry. Methods Mol. Biol., 2010, 612, 335-352.
[http://dx.doi.org/10.1007/978-1-60761-362-6_23] [PMID: 20033652]
[14]
Vivier, E.; Tomasello, E.; Baratin, M.; Walzer, T.; Ugolini, S. Functions of natural killer cells. Nat. Immunol., 2008, 9(5), 503-510.
[http://dx.doi.org/10.1038/ni1582] [PMID: 18425107]
[15]
Raulet, D.H. Interplay of natural killer cells and their receptors with the adaptive immune response. Nat. Immunol., 2004, 5(10), 996-1002.
[http://dx.doi.org/10.1038/ni1114] [PMID: 15454923]
[16]
Strowig, T.; Brilot, F.; Münz, C. Noncytotoxic functions of NK cells: Direct pathogen restriction and assistance to adaptive immunity. J. Immunol., 2008, 180(12), 7785-7791.
[http://dx.doi.org/10.4049/jimmunol.180.12.7785] [PMID: 18523242]
[17]
Crinier, A.; Narni-Mancinelli, E.; Ugolini, S.; Vivier, E. SnapShot: Natural killer cells. Cell, 2020, 180(6), 1280-1280.e1.
[http://dx.doi.org/10.1016/j.cell.2020.02.029] [PMID: 32200803]
[18]
Hodgins, J.J.; Khan, S.T.; Park, M.M.; Auer, R.C.; Ardolino, M. Killers 2.0: NK cell therapies at the forefront of cancer control. J. Clin. Invest., 2019, 129(9), 3499-3510.
[http://dx.doi.org/10.1172/JCI129338] [PMID: 31478911]
[19]
Bonamichi, B.D.S.F.; Lee, J. Unusual Suspects in the Development of Obesity-Induced Inflammation and Insulin Resistance: NK cells, iNKT cells, and ILCs. Diabetes Metab. J., 2017, 41(4), 229-250.
[http://dx.doi.org/10.4093/dmj.2017.41.4.229] [PMID: 28537058]
[20]
Vivier, E.; Raulet, D.H.; Moretta, A.; Caligiuri, M.A.; Zitvogel, L.; Lanier, L.L.; Yokoyama, W.M.; Ugolini, S. Innate or adaptive immunity? The example of natural killer cells. Science, 2011, 331(6013), 44-49.
[http://dx.doi.org/10.1126/science.1198687] [PMID: 21212348]
[21]
O’Sullivan, T.E.; Sun, J.C.; Lanier, L.L. Natural Killer Cell Memory. Immunity, 2015, 43(4), 634-645.
[http://dx.doi.org/10.1016/j.immuni.2015.09.013] [PMID: 26488815]
[22]
Suto, H; Nambu, A; Morita, H; Yamaguchi, S; Numata, T; Yoshizaki, T; Shimura, E; Arae, K; Asada, Y; Motomura, K; Kaneko, M; Takaya, A; Matsuda, A; Iwakura, Y; Okumura, K; Saito, H; Matsumoto, K; Sudo, K; Nakae, S IL-25 enhances TH17 cell-mediated contact dermatitis by promoting IL-1beta production by dermal dendritic cells. J Allergy Clin Immunol., 2018, 142(5), 1500-1509.e10.
[23]
Zhang, Y.; Wang, Y.; Li, M.Q.; Duan, J.; Fan, D.X.; Jin, L.P. IL-25 promotes Th2 bias by upregulating IL-4 and IL-10 expression of decidual γδT cells in early pregnancy. Exp. Ther. Med., 2018, 15(2), 1855-1862.
[PMID: 29434775]
[24]
Hams, E.; Locksley, R.M.; McKenzie, A.N.J.; Fallon, P.G. Cutting edge: IL-25 elicits innate lymphoid type 2 and type II NKT cells that regulate obesity in mice. J. Immunol., 2013, 191(11), 5349-5353.
[http://dx.doi.org/10.4049/jimmunol.1301176] [PMID: 24166975]
[25]
Cai, T.; Qiu, J.; Ji, Y.; Li, W.; Ding, Z.; Suo, C.; Chang, J.; Wang, J.; He, R.; Qian, Y.; Guo, X.; Zhou, L.; Sheng, H.; Shen, L.; Qiu, J. IL-17–producing ST2+ group 2 innate lymphoid cells play a pathogenic role in lung inflammation. J. Allergy Clin. Immunol., 2019, 143(1), 229-244.e9.
[http://dx.doi.org/10.1016/j.jaci.2018.03.007] [PMID: 29625134]
[26]
Li, Q.; Ma, L.; Shen, S.; Guo, Y.; Cao, Q.; Cai, X.; Feng, J.; Yan, Y.; Hu, T.; Luo, S.; Zhou, L.; Peng, B.; Yang, Z.; Hua, Y. Intestinal dysbacteriosis-induced IL-25 promotes development of HCC via alternative activation of macrophages in tumor microenvironment. J. Exp. Clin. Cancer Res., 2019, 38(1), 303.
[http://dx.doi.org/10.1186/s13046-019-1271-3] [PMID: 31296243]
[27]
Wiśniewski, J.R.; Zougman, A.; Nagaraj, N.; Mann, M. Universal sample preparation method for proteome analysis. Nat. Methods, 2009, 6(5), 359-362.
[http://dx.doi.org/10.1038/nmeth.1322] [PMID: 19377485]
[28]
Wang, Y.; Zhang, J.; Song, W.; Tian, X.; Liu, Y.; Wang, Y.; Ma, J.; Wang, C.; Yan, G. A proteomic analysis of urine biomarkers in autism spectrum disorder. J. Proteomics, 2021, 242, 104259.
[http://dx.doi.org/10.1016/j.jprot.2021.104259] [PMID: 33957315]
[29]
Cox, J.; Neuhauser, N.; Michalski, A.; Scheltema, R.A.; Olsen, J.V.; Mann, M. Andromeda: A peptide search engine integrated into the MaxQuant environment. J. Proteome Res., 2011, 10(4), 1794-1805.
[http://dx.doi.org/10.1021/pr101065j] [PMID: 21254760]
[30]
Kanehisa, M.; Goto, S.; Sato, Y.; Furumichi, M.; Tanabe, M. KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Res., 2012, 40(D1), D109-D114.
[http://dx.doi.org/10.1093/nar/gkr988] [PMID: 22080510]
[31]
Jelenčić, V.; Šestan, M.; Kavazović, I.; Lenartić, M.; Marinović, S.; Holmes, T.D.; Prchal-Murphy, M.; Lisnić, B.; Sexl, V.; Bryceson, Y.T.; Wensveen, F.M.; Polić, B. NK cell receptor NKG2D sets activation threshold for the NCR1 receptor early in NK cell development. Nat. Immunol., 2018, 19(10), 1083-1092.
[http://dx.doi.org/10.1038/s41590-018-0209-9] [PMID: 30224819]
[32]
Kim, T.D.; Lee, S.U.; Yun, S.; Sun, H.N.; Lee, S.H.; Kim, J.W.; Kim, H.M.; Park, S.K.; Lee, C.W.; Yoon, S.R.; Greenberg, P.D.; Choi, I. Human microRNA-27a* targets Prf1 and GzmB expres- sion to regulate NK-cell cytotoxicity. Blood, 2011, 118(20), 5476-5486.
[http://dx.doi.org/10.1182/blood-2011-04-347526] [PMID: 21960590]
[33]
Bexte, T.; Alzubi, J.; Reindl, L.M.; Wendel, P.; Schubert, R.; Salzmann-Manrique, E.; von Metzler, I.; Cathomen, T.; Ullrich, E. CRISPR-Cas9 based gene editing of the immune checkpoint NKG2A enhances NK cell mediated cytotoxicity against multiple myeloma. OncoImmunology, 2022, 11(1), 2081415.
[http://dx.doi.org/10.1080/2162402X.2022.2081415] [PMID: 35694192]
[34]
Knapp-Wilson, A.; Pereira, G.C.; Buzzard, E.; Ford, H.C.; Richardson, A.; Corey, R.A.; Neal, C.; Verkade, P.; Halestrap, A.P.; Gold, V.A.M.; Kuwabara, P.E.; Collinson, I. Maintenance of complex I and its supercomplexes by NDUF-11 is essential for mitochondrial structure, function and health. J. Cell Sci., 2021, 134(13), jcs258399.
[http://dx.doi.org/10.1242/jcs.258399] [PMID: 34106255]
[35]
Melegari, M.; Scaglioni, P.P.; Wands, J.R. Cloning and characterization of a novel hepatitis B virus x binding protein that inhibits viral replication. J. Virol., 1998, 72(3), 1737-1743.
[http://dx.doi.org/10.1128/JVI.72.3.1737-1743.1998] [PMID: 9499022]
[36]
Li, Y.; Wang, Z.; Shi, H.; Li, H.; Li, L.; Fang, R.; Cai, X.; Liu, B.; Zhang, X.; Ye, L. HBXIP and LSD1 Scaffolded by lncRNA Hotair Mediate Transcriptional Activation by c-Myc. Cancer Res., 2016, 76(2), 293-304.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-3607] [PMID: 26719542]
[37]
Zhang, W.; Zhuang, N.; Liu, X.; He, L.; He, Y.; Mahinthichaichan, P.; Zhang, H.; Kang, Y.; Lu, Y.; Wu, Q.; Xu, D.; Shi, L. The metabolic regulator Lamtor5 suppresses inflammatory signaling via regulating mTOR-mediated TLR4 degradation. Cell. Mol. Immunol., 2020, 17(10), 1063-1076.
[http://dx.doi.org/10.1038/s41423-019-0281-6] [PMID: 31467416]
[38]
Tayanloo-Beik, A.; Sarvari, M.; Payab, M.; Gilany, K.; Alavi-Moghadam, S.; Gholami, M.; Goodarzi, P.; Larijani, B.; Arjmand, B. OMICS insights into cancer histology; Metabolomics and proteomics approach. Clin. Biochem., 2020, 84, 13-20.
[http://dx.doi.org/10.1016/j.clinbiochem.2020.06.008] [PMID: 32589887]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy