Effects of adipose-derived stem cells and non-methylated CpG-oligodeoxynucleotides on peripheral blood CD4+CD25+ regulatory T cells in young mice with food allergy
CHEN Xu-Lin1, ZHENG Cheng-Zhong1,2
Department of Pediatrics, 306 th Clinical College of People's Liberation Army, Anhui Medical University, Hefei 230032, China
Abstract：Objective To investigate the effects of adipose-derived stem cells (ADSC) and non-methylated CpG-oligodeoxynucleotides (CpG-ODN) on the expression of peripheral blood CD4+CD25+ regulatory T (Treg) cells in young mice with food allergy, as well as their immune intervention effects. Methods A total of 40 female BALB/c mice were randomly divided into control group, allergic group, ADSC treatment group, and CpG-ODN treatment group, with 10 mice in each group. A mouse model of food allergy was established by intraperitoneal injection and intragastric administration of ovalbumin (OVA) for sensitization and challenge. The mice in the control group were treated with normal saline at the same dose; the mice in the ADSC treatment group were given intraperitoneal injection of ADSC (1×106 cells for each mouse) before and after OVA challenge, and those in the CpG-ODN treatment group were given intraperitoneal injection of non-methylated CpG-ODN solution (40 μg for each mouse) at 1 hour before challenge by gavage. The allergic symptom scores were determined for each group after model establishment. ELISA was used to measure the serum level of OVA-IgE. Flow cytometry was used to measure the percentage of peripheral blood CD4+CD25+ Treg cells. Hematoxylin and eosin staining was used for the pathological analysis of the jejunum. Results The allergic group had significantly higher allergic symptom scores and serum level of OVA-IgE than the control group (P P > 0.05), but these two groups had significantly lower allergic symptom scores and serum level of OVA-IgE than the allergic group and significantly higher allergic symptom scores and serum level of OVA-IgE than the control group (P +CD25+ Treg cells than the control group (P +CD25+ Treg cells than the allergic group (P P > 0.05). Pathological results showed structural damage and edema in the jejunal villi, a large number of eosinophils, and lymphocyte infiltration in the allergic group, while the ADSC treatment group and the CpG-ODN treatment group had less structural damage and edema in the jejunal villi, a lower number of eosinophils, and less lymphocyte infiltration. Conclusions ADSC and non-methylated CpG-ODN have a certain effect in the treatment of food allergy and can increase the percentage of peripheral blood CD4+CD25+ Treg cells and reduce the level of OVA-IgE. They may be associated with the induction of immune tolerance and these two treatment have comparable effects. Detailed mechanisms of action still need further investigation.
CHEN Xu-Lin,ZHENG Cheng-Zhong. Effects of adipose-derived stem cells and non-methylated CpG-oligodeoxynucleotides on peripheral blood CD4+CD25+ regulatory T cells in young mice with food allergy[J]. CJCP, 2017, 19(5): 590-595.
Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy:multiple suppressor factors at work in immune tolerance to allergens[J]. J Allergy Clin Immunol, 2014, 133(3):621-631.
[2]
Sakaguchi S, Sakaguchi N, Assno M, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25)[J]. J Immunol, 1995, 155(3):1151-1164.
Dasgupta A, Saxena R. Regulatory T cells:a review[J]. Natl Med J India, 2012, 25(6):341-351.
[7]
Shalev I, Schmelzle M, Robson SC, et al. Making sense of regulatory T cell suppressive function[J]. Semin Immunol, 2011, 23(4):282-292.
[8]
Mavinkurve-Groothuis AM, Marcus KA, Pourier M, et al. Myocardial 2D strain echocardiography and cardiac biomarkers in children during and shortly after anthracycline therapy for acute lymphoblastic leukaemia(ALL):a prospective study[J]. Eur Heart J Cardiovasc Imaging, 2013, 14(6):562-569.
James S, Fox J, Afsari F, et al. Multiparameter analysis of human bone marrow stromal cells identifies distinct immunomodulatory and differentiation-competent subtypes[J]. Stem Cell Reports, 2015, 4(6):1004-1015.
[11]
Fan L, Yu Z, Li J, et al. Immunoregulation effects of bone marrow-derived mesenchymal stem cells in xenogeneic acellular nerve grafts transplant[J]. Cell Mol Neurobiol, 2014, 34(7):999-1010.
Hofmann U, Frantz S. How can we cure a heart "in flame"? A translational view on inflammation in heart failure[J]. Basic Res Cardiol, 2013, 108(4):356.
Nemeth K, Keane-Myers A, Brown JM, et al. Bone marrow stromal cells use TGF-beta to suppress allergic responses in a mouse model of ragweed-induced asthma[J]. Proc Natl Acad Sci U S A, 2010, 107(12):5652-5657.
Urry Z, Xystrakis E, Richards DF, et al. Ligation of TLR9 induced on human IL-10-secreting Tregs by 1 alpha, 25-dihydroxyvitamin D3 abrogates regulatory function[J]. J Clin Invest, 2009, 119(2):387-398.
