Effect of transduced mesenchymal stem cells with IL-10 gene on control of allergic asthma
Main Article Content
Keywords
Cell therapy, Gene therapy, Allergy, Inflammation, Cytokine
Abstract
Asthma is an important pulmonary disease associated with T helper lymphocyte (Th)2 dominant immune response, which can initiate allergic and inflammatory reactions. Interleukin (IL)-10 is the main immune suppressor cytokine, and mesenchymal stem cells (MSCs) have an immune-modulatory potential that can be transduced with the expression of the IL-10 gene to control pathophysiology of allergic asthma. Bone marrow’s MSCs were isolated and transduced with the expression vector that contains the expressible IL-10 gene. Then, allergic asthma mouse model was produced and treated with manipulated MSCs. Methacholine challenge test; measurement of IL-4, IL-5, IL-8, IL-13, IL-25, and IL-33; and total and ovalbumin (OVA)-specific immunoglobulin (Ig)E levels were done. Hyperplasia of the goblet cell, secretion of mucus, and peribronchiolar and perivascular eosinophilic inflammation were evaluated in lung pathological sections. IL-25, IL-33, and total IgE levels; AHR; eosinophilic inflammation; hyperplasia of the goblet cell; and secretion of mucus could be controlled in M, MV, and MV-10 groups, and the control in the MV-10 group was strong compared to M and MV groups. MSCs have immune-modulatory capacity that can control allergic asthma pathophysiology, and this effect can be strengthened and reinforced by the expression of IL-10 gene.
References
1. Jinan J, Entezar MN, Seyyede MA, Seyyed SA. Effects of vitamin E and selenium on allergic rhinitis and asthma pathophysiology. Respir Phys & Neuro. 2021;286:103614. 10.1016/j.resp.2020.103614
2. Kamran BL, Behnam H, Seyyed SA. The mechanisms underlying Helicobacter Pylori-mediated protection against allergic asthma. Tanaffos. 2017;16(4):251–259.
3. Masoume AS, Mehrabi NE, Shamsadin AS. Study effect of Ocimum basilicum seeds on mucus production and cytokine gene expression in allergic asthma mice model. Revue Francaise d'Allergologie 2018;58(7):489–493. 10.1016/j.reval.2018.08.003
4. Baowei M, Seyyed SA, Entezar MN, Limin Z. PI3K/AKT/mTOR and TLR4/MyD88/NF-κB Signaling Inhibitors Attenuate Pathological Mechanisms of Allergic Asthma. Inflam. 2021;44(5):1895–1907. 10.1007/s10753-021-01466-3
5. Hami M, Naddaf S, Mobedi I, Zare-Bidaki M, Athari S, Hajimohammadi B, Anaraki-Mohammadi G. Prevalence of Linguatula serrata infection in domestic bovids slaughtered in Tabriz Abattoir, Iran. Iranian J of Parasit. 2009;4(3):25–31.
6. Hajimohammadi B, Athari SM, Abdollahi M, Vahedi G and Athari SS. Oral Administration of Acrylamide Worsens the Inflammatory Responses in the Airways of Asthmatic Mice through Agitation of Oxidative Stress in the Lungs. Frontiers in Immun. 2020;11:1940. 10.3389/fimmu.2020.01940
7. Yousri MH, Sally MS, Randa HM, Tamer HH. Association between genes encoding components of the IL-10/IL-0 receptor pathway and asthma in children. Ann Allergy Asthma Immunol. 2011;106:474–48. 10.1016/j.anai.2011.02.021
8. Wei W, Yibo Z, Yan Z, Heng J, Songtao S. The role of IL-10 in kidney disease. Inter Immuno. 2022;108:108917. 10.1016/j.intimp.2022.108917
9. Andreas RRW, Marc HD. Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs. Front Immunol. 2019;10:1191. 10.3389/fimmu.2019.01191
10. Xiang-Hua B, Feng G, Seyyed SA, Hongqun W. Immuno-modulatory effect of IL-35 gene-transfected mesenchymal stem cells on allergic asthma. Fundam Clin Pharmacol. 2022. 10.1111/fcp.12823
11. Minmin H, Entezar MN, Seyyed SA. Immunoregulatory effect of mesenchymal stem cell via mitochondria signaling pathways in allergic asthma. Saudi J of Biolo Sci. 2021;28:6957–6962. 10.1016/j.sjbs.2021.07.071
12. Yan L, Xiuhe P, Xiao P, Shubo L, Yanchun Z, Xiaoxuan Z, Mingcai L, Mingcai L. Adenovirus-mediated interleukin-35 gene transfer suppresses allergic airway inflammation in a murine model of asthma. Inflamm Res. 2015; 64(10):767–74. 10.1007/s00011-015-0858-1
13. Xing Z, Ohkawara Y, Jordana M, Graham FL, Gauldie J. Adenoviral vector-mediated interleukin-10 expression in vivo: intramuscular gene transfer inhibits cytokine responses in endotoxemia. Gene Therapy 1997;4:140–149. 10.1038/sj.gt.3300371
14. Chung F. Anti-inflammatory cytokines in asthma and allergy: interleukin10, interleukin-12, interferon-gamma. Mediators Inflamm. 2001;10:51–59. 10.1080/09629350120054518
15. Yang L, Lian X, Cowen A, Xu H, Du H, Yan C. Synergy between STAT3 and RAR-alpha in regulation of the surfactant protein B gene in the lung. Mol Endocrinol. 2004;18:1520–1532. 10.1210/me.2003-0458
16. Cazes E, Giron-Michel J, Baouz S, et al. Novel anti-inflammatory effects of the inhaled corticosteroid fluticasone propionate during lung myofibroblastic differentiation. J Immunol. 2001;167:5329–5337. 10.4049/jimmunol.167.9.5329
17. Knight D, Mutsaers SE, Prêle CM. STAT3 in tissue fibrosis: is there a role in the lung? Pulm Pharmacol Ther. 2010-2012; 1–624(2):193–198. 10.1016/j.pupt.2010.10.005
18. Pitrez PM, Gualdi LP, Barbosa GL, Sudbrack S, Ponzi D, Cao RG, et al. Effect of different helminth extracts on the development of asthma in mice: The influence of early-life exposure and the role of IL-10 response. Exper Parasit. 2015;156:95–103. 10.1016/j.exppara.2015.06.004
19. Jiling R, Yongzhe L, Ye Y, Lifeng F, Xiaotong Z, Zongjin L, Liang Y. Intranasal delivery of MSC-derived exosomes attenuates allergic asthma via expanding IL-10 producing lung interstitial macrophages in mice. Inter Immunop. 2021;91:107288. 10.1016/j.intimp.2020.107288
20. Zeng SL, Wang LH, Li P, Wang W, Yang J. Mesenchymal stem cells abrogate experimental asthma by altering dendritic cell function. Mol. Med. Rep. 2015;12(2):2511–2520. 10.3892/mmr.2015.3706
21. Li Y, Li H, Cao Y, Wu F, Ma W, Wang Y, Sun S. Placenta-derived mesenchymal stem cells improve airway hyperresponsiveness and inflammation in asthmatic rats by modulating the Th17/Treg balance, Mol. Med. Rep. 2017;16(6):8137–8145. 10.3892/mmr.2017.7605
22. Braza F, Dirou S, Forest V, Sauzeau V, Hassoun D, Chesne J, Cheminant-Muller MA et al. Mesenchymal stem cells induce suppressive macrophages through phagocytosis in a mouse model of asthma. Stem Cells 2016;34(7):1836–1845. 10.1002/stem.2344
23. Chu-Lun L, George H, Ching-Chiung W, Yueh-Lun L. Imperatorin exerts antiallergic effects in Th2-mediated allergic asthma via induction of IL-10-producing regulatory T cells by modulating the function of dendritic cells. Pharma Res. 2016;110:111–121. 10.1016/j.phrs.2016.04.030
24. Metenou S, Nutman TB. Regulatory T cell subsets in filarial infection and their function. Front. Immunol. 2013;4:305. 10.3389/fimmu.2013.00305
25. Pelaia F, Vatrella A, Busceti MT, Gallelli L, Calabrese C, Terracciano R, et al. Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma. Mediators Inflamm. 2015;2015:879783. 10.1155/2015/879783
26. Kasaian MT, Marquette K, Fish S, DeClercq C, Agostinelli R, Cook TA, et al. An IL-4/IL-13 dual antagonist reduces lung inflammation, airway hyperresponsiveness, and IgE production in mice. Am J. Respir Cell Mol Biol. 2013;49:37–46. 10.1165/rcmb.2012-0500OC
27. William JB, Helen S, Robert AO, Simone AW, Franz P, Lisa GG, et al. A T cell–myeloid IL-10 axis regulates pathogenic IFN-g–dependent immunity in a mouse model of type 2–low asthma. J of Allergy & Clin Immunol. 2020;145(2):666–678. 10.1016/j.jaci.2019.08.006
28. Faisal M, Sebastian L, Edward M, Rebecca J, Kevin C, Stamatia P, et al. The Generation of an Engineered Interleukin-10 Protein with Improved Stability and Biological Function. Front. Immunol. 2020;11:1794. 10.3389/fimmu.2020.01794
29. Joost LMV, Betty CAM, Gerard AH, Martien LK, Frank RW, Antoon JM. Allergen immunotherapy induces a suppressive memory response mediated by IL-10 in a mouse asthma model. J Allergy Clin Immunol. 2004;113(6):1204–1210. 10.1016/j.jaci.2004.02.041
30. Christian MH, Jay HB. Cell type-specific regulation of IL-10 expression in inflammation and disease. Immunol. Res. 2010;47(1–3):185–206. 10.1007/s12026-009-8150-5
31. Katsuyuki T, Sam L, Toyoyuki H, Omar U, Rob S, Fan CK, et al. Attenuated production of intracellular IL-10 and IL-12 in Monocytes from patients with severe asthma. Clin Immunol. 2002;102(3):258–266. 10.1006/clim.2001.5176
2. Kamran BL, Behnam H, Seyyed SA. The mechanisms underlying Helicobacter Pylori-mediated protection against allergic asthma. Tanaffos. 2017;16(4):251–259.
3. Masoume AS, Mehrabi NE, Shamsadin AS. Study effect of Ocimum basilicum seeds on mucus production and cytokine gene expression in allergic asthma mice model. Revue Francaise d'Allergologie 2018;58(7):489–493. 10.1016/j.reval.2018.08.003
4. Baowei M, Seyyed SA, Entezar MN, Limin Z. PI3K/AKT/mTOR and TLR4/MyD88/NF-κB Signaling Inhibitors Attenuate Pathological Mechanisms of Allergic Asthma. Inflam. 2021;44(5):1895–1907. 10.1007/s10753-021-01466-3
5. Hami M, Naddaf S, Mobedi I, Zare-Bidaki M, Athari S, Hajimohammadi B, Anaraki-Mohammadi G. Prevalence of Linguatula serrata infection in domestic bovids slaughtered in Tabriz Abattoir, Iran. Iranian J of Parasit. 2009;4(3):25–31.
6. Hajimohammadi B, Athari SM, Abdollahi M, Vahedi G and Athari SS. Oral Administration of Acrylamide Worsens the Inflammatory Responses in the Airways of Asthmatic Mice through Agitation of Oxidative Stress in the Lungs. Frontiers in Immun. 2020;11:1940. 10.3389/fimmu.2020.01940
7. Yousri MH, Sally MS, Randa HM, Tamer HH. Association between genes encoding components of the IL-10/IL-0 receptor pathway and asthma in children. Ann Allergy Asthma Immunol. 2011;106:474–48. 10.1016/j.anai.2011.02.021
8. Wei W, Yibo Z, Yan Z, Heng J, Songtao S. The role of IL-10 in kidney disease. Inter Immuno. 2022;108:108917. 10.1016/j.intimp.2022.108917
9. Andreas RRW, Marc HD. Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs. Front Immunol. 2019;10:1191. 10.3389/fimmu.2019.01191
10. Xiang-Hua B, Feng G, Seyyed SA, Hongqun W. Immuno-modulatory effect of IL-35 gene-transfected mesenchymal stem cells on allergic asthma. Fundam Clin Pharmacol. 2022. 10.1111/fcp.12823
11. Minmin H, Entezar MN, Seyyed SA. Immunoregulatory effect of mesenchymal stem cell via mitochondria signaling pathways in allergic asthma. Saudi J of Biolo Sci. 2021;28:6957–6962. 10.1016/j.sjbs.2021.07.071
12. Yan L, Xiuhe P, Xiao P, Shubo L, Yanchun Z, Xiaoxuan Z, Mingcai L, Mingcai L. Adenovirus-mediated interleukin-35 gene transfer suppresses allergic airway inflammation in a murine model of asthma. Inflamm Res. 2015; 64(10):767–74. 10.1007/s00011-015-0858-1
13. Xing Z, Ohkawara Y, Jordana M, Graham FL, Gauldie J. Adenoviral vector-mediated interleukin-10 expression in vivo: intramuscular gene transfer inhibits cytokine responses in endotoxemia. Gene Therapy 1997;4:140–149. 10.1038/sj.gt.3300371
14. Chung F. Anti-inflammatory cytokines in asthma and allergy: interleukin10, interleukin-12, interferon-gamma. Mediators Inflamm. 2001;10:51–59. 10.1080/09629350120054518
15. Yang L, Lian X, Cowen A, Xu H, Du H, Yan C. Synergy between STAT3 and RAR-alpha in regulation of the surfactant protein B gene in the lung. Mol Endocrinol. 2004;18:1520–1532. 10.1210/me.2003-0458
16. Cazes E, Giron-Michel J, Baouz S, et al. Novel anti-inflammatory effects of the inhaled corticosteroid fluticasone propionate during lung myofibroblastic differentiation. J Immunol. 2001;167:5329–5337. 10.4049/jimmunol.167.9.5329
17. Knight D, Mutsaers SE, Prêle CM. STAT3 in tissue fibrosis: is there a role in the lung? Pulm Pharmacol Ther. 2010-2012; 1–624(2):193–198. 10.1016/j.pupt.2010.10.005
18. Pitrez PM, Gualdi LP, Barbosa GL, Sudbrack S, Ponzi D, Cao RG, et al. Effect of different helminth extracts on the development of asthma in mice: The influence of early-life exposure and the role of IL-10 response. Exper Parasit. 2015;156:95–103. 10.1016/j.exppara.2015.06.004
19. Jiling R, Yongzhe L, Ye Y, Lifeng F, Xiaotong Z, Zongjin L, Liang Y. Intranasal delivery of MSC-derived exosomes attenuates allergic asthma via expanding IL-10 producing lung interstitial macrophages in mice. Inter Immunop. 2021;91:107288. 10.1016/j.intimp.2020.107288
20. Zeng SL, Wang LH, Li P, Wang W, Yang J. Mesenchymal stem cells abrogate experimental asthma by altering dendritic cell function. Mol. Med. Rep. 2015;12(2):2511–2520. 10.3892/mmr.2015.3706
21. Li Y, Li H, Cao Y, Wu F, Ma W, Wang Y, Sun S. Placenta-derived mesenchymal stem cells improve airway hyperresponsiveness and inflammation in asthmatic rats by modulating the Th17/Treg balance, Mol. Med. Rep. 2017;16(6):8137–8145. 10.3892/mmr.2017.7605
22. Braza F, Dirou S, Forest V, Sauzeau V, Hassoun D, Chesne J, Cheminant-Muller MA et al. Mesenchymal stem cells induce suppressive macrophages through phagocytosis in a mouse model of asthma. Stem Cells 2016;34(7):1836–1845. 10.1002/stem.2344
23. Chu-Lun L, George H, Ching-Chiung W, Yueh-Lun L. Imperatorin exerts antiallergic effects in Th2-mediated allergic asthma via induction of IL-10-producing regulatory T cells by modulating the function of dendritic cells. Pharma Res. 2016;110:111–121. 10.1016/j.phrs.2016.04.030
24. Metenou S, Nutman TB. Regulatory T cell subsets in filarial infection and their function. Front. Immunol. 2013;4:305. 10.3389/fimmu.2013.00305
25. Pelaia F, Vatrella A, Busceti MT, Gallelli L, Calabrese C, Terracciano R, et al. Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma. Mediators Inflamm. 2015;2015:879783. 10.1155/2015/879783
26. Kasaian MT, Marquette K, Fish S, DeClercq C, Agostinelli R, Cook TA, et al. An IL-4/IL-13 dual antagonist reduces lung inflammation, airway hyperresponsiveness, and IgE production in mice. Am J. Respir Cell Mol Biol. 2013;49:37–46. 10.1165/rcmb.2012-0500OC
27. William JB, Helen S, Robert AO, Simone AW, Franz P, Lisa GG, et al. A T cell–myeloid IL-10 axis regulates pathogenic IFN-g–dependent immunity in a mouse model of type 2–low asthma. J of Allergy & Clin Immunol. 2020;145(2):666–678. 10.1016/j.jaci.2019.08.006
28. Faisal M, Sebastian L, Edward M, Rebecca J, Kevin C, Stamatia P, et al. The Generation of an Engineered Interleukin-10 Protein with Improved Stability and Biological Function. Front. Immunol. 2020;11:1794. 10.3389/fimmu.2020.01794
29. Joost LMV, Betty CAM, Gerard AH, Martien LK, Frank RW, Antoon JM. Allergen immunotherapy induces a suppressive memory response mediated by IL-10 in a mouse asthma model. J Allergy Clin Immunol. 2004;113(6):1204–1210. 10.1016/j.jaci.2004.02.041
30. Christian MH, Jay HB. Cell type-specific regulation of IL-10 expression in inflammation and disease. Immunol. Res. 2010;47(1–3):185–206. 10.1007/s12026-009-8150-5
31. Katsuyuki T, Sam L, Toyoyuki H, Omar U, Rob S, Fan CK, et al. Attenuated production of intracellular IL-10 and IL-12 in Monocytes from patients with severe asthma. Clin Immunol. 2002;102(3):258–266. 10.1006/clim.2001.5176
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