Immunomodulatory effect of IL-2 induced bone marrow mononuclear cell therapy on control of allergic asthma
Main Article Content
Keywords
Scell therapy, immune response, inflammation, lung disease
Abstract
Asthma is a chronic airway disease. Allergic reactions and T helper (h)2 immune response play a key role in asthma occurrence. Cell therapy can control inflammation and remodeling responses in allergic asthma, and cytokines can change this effect. Therefore, in this study, the effect of treated cell therapy with IL-2 to control allergic asthma was studied. Bone marrow cells were extracted and co-cultured with IL-2 and the cells were used via intra-tracheal administration in allergic asthma mice. Levels of IL-4, IL-5, IL-13, Leukotriene B4 and C4, and remodeling factors were measured. At least, a histopathology test of lung tissue was done. Type2 cytokines, leukotrienes, remodeling factors, mucus secretion, goblet cell hyperplasia, peri-bronchial and peri-vascular inflammation were significantly (p˂0.05) decreased by treating with bone marrow-derived mononuclear cells (BMDMCs) and IL-2-BMDMCs. Treatment with IL-2-BMDMCs could significantly decrease IL-13, transforming growth factor (TGF)-β, HP levels, and mucus secretion (p˂0.05) compared to BMDMCs treatment. In this study, BMDMCs and IL-2-BMDMCs therapy could decrease inflammation, allergic, and remodeling factors in allergic asthma. Cell therapy with BMDMCs had a strong and notable effect on the control of allergic asthma pathophysiology when co-cultured and used with IL-2.
References
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24. Sheng-Xiao Zhang, Jia Wang, Cai-Hong Wang, Rui-Huan Jia, Ming Yan, Fang-Yuan Hu, et al. Low-dose IL-2 therapy limits the reduction in absolute numbers of circulating regulatory T cells in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2021;13:1759720X211011370.
25. Zhou P, Chen J, He J, Zheng T, Yunis J, Makota V, et al. Low-dose IL-2 therapy invigorates CD8+ T cells for viral control in systemic lupus erythematosus. PLoS Pathog. 2021;17(10):e1009858. 10.1371/journal.ppat.1009858
26. Minmin Huang, Entezar Mehrabi Nasab, Seyyed Shamsadin Athari. Immunoregulatory effect of mesenchymal stem cell via mitochondria signaling pathways in allergic asthma. Saudi J Biol Sci. 2021;28:6957–62. 10.1016/j.sjbs.2021.07.071
27. Spolski R, Li P, Leonard WJ. Biology and regulation of IL-2: From molecular mechanisms to human therapy. Nat Rev Immunol. 2018;18(10):648–59. 10.1038/s41577-018-0046-y
28. Seyyed Shamsadin Athari. Targeting cell signaling in allergic asthma. Signal Transduct Target Ther. 2019;4:45. 10.1038/s41392-019-0079-0
29. Ling Qian, Entezar Mehrabi Nasab, Seyyede Masoume Athari, Seyyed Shamsadin Athari. Mitochondria signaling pathways in allergic asthma. J Investig Med. 2022;70(4):863–882. 10.1136/jim-2021-002098
2. Masoume Athari S, Mehrabi Nasab E, Shamsadin Athari S. Study effect of Ocimum basilicum seeds on mucus production and cytokine gene expression in allergic asthma mice model. Revue française d’allergologie. 2018;58(7):489–93. 10.1016/j.reval.2018.08.003
3. Baowei Ma, Seyyed Shamsadin Athari, Entezar Mehrabi Nasab, Limin Zhao. PI3K/AKT/mTOR and TLR4/MyD88/NF-κB signaling inhibitors attenuate pathological mechanisms of allergic asthma. Inflammation .2021;44(5):1895–907. 10.1007/s10753-021-01466-3
4. Seyyed Shamsadin Athari, Seyyed Moehyadin Athari. The importance of eosinophil, platelet and dendritic cell in asthma. Asian Pac J Trop Dis. 2014;4(1):41–7. 10.1016/S2222-1808(14)60413-8
5. Mehrabi Nasab E, Athari SM, Motlagh B, Athari SS. Effects of oral administration of Ocimum basilicum on goblet cell hyperplasia and upstream cytokine gene expression in allergic asthma. Revue française d’allergologie. 2020;60:64–8. 10.1016/j.reval.2019.02.226
6. Jinan Jiang, Entezar Mehrabi Nasab, Seyyede Masoume Athari, Seyyed Shamsadin Athari. Effects of vitamin E and selenium on allergic rhinitis and asthma pathophysiology. Respir Physiol Neurobiol. 2021;286:103614. 10.1016/j.resp.2020.103614
7. Soraia C. Abreu, Mariana A. Antunes, Tatiana Maron-Gutierrez, Fernanda F. Cruz, Debora S. Ornellas, Adriana L. Silva, et al. Bone marrow mononuclear cell therapy in experimental allergic asthma: Intratracheal versus intravenous administration. Respir Physiol Neurobiol. 2013;185:615–24. 10.1016/j.resp.2012.11.005
8. Abreu SC, Antunes MA, Maron-Gutierrez T, Cruz FF, Carmo LG, Ornellas DS, et al. Effects of bone marrow-derived mononuclear cells on airway and lung parenchyma remodeling in a murine model of chronic allergic inflammation. Respir Physiol Neurobiol. 2011;175(1):153–63. 10.1016/j.resp.2010.10.006
9. Pengcheng Zhou. Emerging mechanisms and applications of low-dose IL-2 therapy in autoimmunity. Cytokine Growth Factor Rev. 2022;67:80–8. 10.1016/j.cytogfr.2022.06.003
10. Ray JP, Staron MM, Shyer JA, Ho P-C, Marshall HD, Gray SM, et al. The interleukin-2-mTORc1 kinase axis defines the signaling, differentiation, and metabolism of T helper 1 and follicular B helper T cells, Immunity. 2015;43(4):690–702. 10.1016/j.immuni.2015.08.017
11. Cephus J-Y, Stier MT, Fuseini H, Yung JA, Toki S, Bloodworth MH, et al. Testosterone attenuates group 2 innate lymphoid cell--mediated airway inflammation, Cell Rep. 2017;21(9):2487–99. 10.1016/j.celrep.2017.10.110
12. Hondowicz BD, An D, Schenkel JM, Kim KS, Steach HR, Krishnamurty AT, et al. Interleukin-2-dependent -allergen- specific tissue-resident memory cells drive asthma, Immunity.2016;44(1):155–66.10.1016/j.immuni.2015.11.004
13. Corfmat M, Willekens C, Vinit J, Bussone G, Fenaux P, Fain O, et al. MINHEMON, Low dose IL-2 in patients with steroid--dependent dysimmune manifestations associated with myelodysplastic syndromes: Athree-case report, Rheumatology. 2021;60(7):3404–8.10.1093/rheumatology/keaa696
14. Jonathan Chatzkel, Michael J. Schell, Jad Chahoud, Jingsong Zhang, Rohit Jain, Jennifer Swank, et al. Coordinated Pembrolizumab and high dose IL-2 (5-in-a-row schedule) for therapy of metastatic clear cell renal cancer. Clin Genitourinary Cancer. 2022;20(3):252–9. 10.1016/j.clgc.2022.01.010
15. Bahador Hajimohammadi, Seyyede Masoume Athari, Mohammad Abdollahi, Ghasem Vahedi, Seyyed Shamsadin Athari. Oral administration of acrylamide worsens the inflammatory responses in the airways of asthmatic mice through agitation of oxidative stress in the lungs. Front Immunol. 2020;11:1940. 10.3389/fimmu.2020.01940
16. Yong-Dong Lin, Xing-Liang Fan, Hong Zhang, Shu-Bin Fang, Cheng-Lin Li, Meng-Xia Deng, et al. The genes involved in asthma with the treatment of human embryonic stem cell--derived mesenchymal stem cells. Molec Immunol. 2018;95:47–55. 10.1016/j.molimm.2018.01.013
17. Lambrecht BN, Hammad H. The immunology of asthma. Nat Immunol. 2015;16:45–56. 10.1038/ni.3049
18. Gao F, Chiu SM, Motan DA, Zhang Z, Chen L, Ji HL, et al. Mesenchymal stem cells and immunomodulation: Current status and future prospects. Cell Death Dis. 2016;7:e2062. 10.1038/cddis.2015.327
19. Lin WY, Oh SKW, Choo ABH, George AJT. Activated T cells modulate immunosuppression by embryonic-and bone marrow-derived mesenchymal stromal cells through a feedback mechanism. Cytotherapy. 2012;14:274–84. 10.3109/14653249.2011.635853
20. Besnard AG, Guillou N, Tschopp J, Erard F, Couillin I, Iwakura Y, et al. NLRP3 inflammasome is required in murine asthma in the absence of aluminum adjuvant. Allergy. 2011;66(8):1047–57. 10.1111/j.1398-9995.2011.02586.x
21. Antunes MA, Abreu SC, Silva AL, Parra-Cuentas ER, Ab’Saber AM, Capelozzi VL, et al. Sex-specific lung remodeling and inflammation changes in experimental allergic asthma. J Appl Physiol. 2010;109(3):855–63. 10.1152/japplphysiol.00333.2010
22. Bellini A, Marini MA, Bianchetti L, Barczyk M, Schmidt M, Mattoli S. Interleukin (IL)-4, IL-13, and IL-17A differentially affect the profibrotic and proinflammatory functions of fibrocytes from asthmatic patients. Mucosal Immunol. 2011;5(2):140–9. 10.1038/mi.2011.60
23. Le Duff F, Bouaziz J-D, Fontas E, Ticchioni M, Viguier M, Dereure O, et al. Low-dose IL-2 for treating moderate to severe alopecia areata: A 52-week multicenter prospective placebo-controlled study assessing its impact on T regulatory cell and NK cell populations. J Investig Dermatol. 2021;141(4):933–6. 10.1016/j.jid.2020.08.015
24. Sheng-Xiao Zhang, Jia Wang, Cai-Hong Wang, Rui-Huan Jia, Ming Yan, Fang-Yuan Hu, et al. Low-dose IL-2 therapy limits the reduction in absolute numbers of circulating regulatory T cells in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2021;13:1759720X211011370.
25. Zhou P, Chen J, He J, Zheng T, Yunis J, Makota V, et al. Low-dose IL-2 therapy invigorates CD8+ T cells for viral control in systemic lupus erythematosus. PLoS Pathog. 2021;17(10):e1009858. 10.1371/journal.ppat.1009858
26. Minmin Huang, Entezar Mehrabi Nasab, Seyyed Shamsadin Athari. Immunoregulatory effect of mesenchymal stem cell via mitochondria signaling pathways in allergic asthma. Saudi J Biol Sci. 2021;28:6957–62. 10.1016/j.sjbs.2021.07.071
27. Spolski R, Li P, Leonard WJ. Biology and regulation of IL-2: From molecular mechanisms to human therapy. Nat Rev Immunol. 2018;18(10):648–59. 10.1038/s41577-018-0046-y
28. Seyyed Shamsadin Athari. Targeting cell signaling in allergic asthma. Signal Transduct Target Ther. 2019;4:45. 10.1038/s41392-019-0079-0
29. Ling Qian, Entezar Mehrabi Nasab, Seyyede Masoume Athari, Seyyed Shamsadin Athari. Mitochondria signaling pathways in allergic asthma. J Investig Med. 2022;70(4):863–882. 10.1136/jim-2021-002098
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