@article { author = {Langroudi, Ladan and Hassan, Zuhair Muhammad and Soleimani, Masoud and Hashemi, Seyed Mahmoud}, title = {Tumor Associated Mesenchymal Stromal Cells Show Higher Immunosuppressive and Angiogenic Properties Compared to Adipose Derived MSCs}, journal = {Iranian Journal of Immunology}, volume = {12}, number = {4}, pages = {226-239}, year = {2015}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {}, abstract = {Background: Differentiation, migratory properties and availability of Mesenchymal Stromal Cells (MSC) have become an important part of biomedical research. However, the functional heterogeneity of cells derived from different tissues has hampered providing definitive phenotypic markers for these cells. Objective: To characterize and compare the phenotype and cytokines of adipose derived MSCs (AD-MSCs) and tumoral-MSCs (T-MSCs) isolated from mammary tumors of BALB/c mice. Methods: Immunophenotyping and in vitro differentiation tests were used for MSC characterization. Cytokine and enzyme profiles were assessed using ELISA and Realtime PCR, respectively. Results: T-MSCs expressed significantly higher levels of HLADR (p=0.04). Higher levels of PGE2 and COX-2 enzyme were also observed in TMSCs (p=0.07 and p=0.00, respectively). Additionally, T-MSCs expressed higher levels of iNOS and MMP9 (p=0.01 and p=0.01, respectively). T-MSCs were also able to induce higher levels of proliferation and migration of HUVEC endothelial cells in wound scratch assay compared to AD-MSCs (p=0.015). Conclusion: Functional differences showed by the surface markers of MSCs, cytokine and enzyme production indicate the effect of different microenvironments on MSCs phenotype and function.}, keywords = {Adipose-Derived Mesenchymal Stromal Cells,Breast cancer,Immunomodulatory Properties,Tumoral-MSCs}, url = {https://iji.sums.ac.ir/article_16752.html}, eprint = {https://iji.sums.ac.ir/article_16752_d84d806bc2cd96fa325eb07adc3d33a6.pdf} } @article { author = {Aghili, Babak and Amirzargar, Ali Akbar and Rajab, Asadollah and Rabbani, Ali and Sotoudeh, Arya and Assadiasl, Sara and Larijani, Bagher and Massoud, Ahmad}, title = {Altered Suppressor Function of Regulatory T Cells in Type 1 Diabetes}, journal = {Iranian Journal of Immunology}, volume = {12}, number = {4}, pages = {240-251}, year = {2015}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {}, abstract = {Background: Type 1 diabetes (T1D) is a T cell mediated autoimmune disease targeting the insulin-producing β cells within pancreatic islets. Autoimmune diseases may develop as a consequence of altered balance between regulatory (Tregs) and autoreactive T cells. Objectives: To evaluate Treg cells frequency and suppressive function in the peripheral blood of newly diagnosed T1D patients in comparison with healthy controls. Methods: Fifteen new cases of T1D patients and 15 age- and sexmatched healthy controls were recruited to this study. Their peripheral blood mononuclear cells (PBMCs) were isolated and CD4 +CD25+FoxP3+CD127-/low Treg cells were studied by flowcytometry technique. Thereafter, Tregs were isolated by Magnetic- Activated Cell Separation (MACS) technology and by using CFSE (carboxyfluorescein succinimidyl ester) dilution assay, their suppressive activity was evaluated in the coculture of CD4 +CD25- T responder cells with Treg cells. Results: The percentage of CD4 +CD25+FoxP3+CD127-/low Tregs did not differ between T1D patients and healthy controls but the MFI (mean fluorescence intensity) of transcription factor FoxP3 (forkhead box protein P3) was significantly decreased in T1D patients (20.03 ± 1.4 vs. 31.33 ± 2.95, p=0.0017). Moreover, the suppressive function of CD4 +CD25+CD127-/low Treg cells was significantly diminished in T1D patients in comparison with control group (35.16 ± 4.93% vs. 60.45 ± 5.26%, respectively, p=0.0015). Conclusion: Present study indicates an impaired immune regulation among T1D patients, characterized by defects in suppressive function and expression of FoxP3 in Treg cells without any significant decrease in their frequency in peripheral blood.}, keywords = {Regulatory T Cells (Tregs),Suppressive Function,(T1D),Type 1 Diabetes}, url = {https://iji.sums.ac.ir/article_16753.html}, eprint = {https://iji.sums.ac.ir/article_16753_babc63ff6b42a4cd066e054e8cdad6fe.pdf} } @article { author = {Rafiee, Mitra and Gharagozloo, Marjan and Ghahiri, Ataollah and Mehrabian, Ferdous and Maracy, Mohammad R. and Kouhpayeh, Shirin and Pieper, Ina Laura and Rezaei, Abbas}, title = {Altered Th17/Treg Ratio in Recurrent Miscarriage after Treatment with Paternal Lymphocytes and Vitamin D3: a Double- Blind Placebo-Controlled Study}, journal = {Iranian Journal of Immunology}, volume = {12}, number = {4}, pages = {252-262}, year = {2015}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {}, abstract = {Background: Recurrent miscarriage (RM) affects 2-5% of pregnant women. Paternal lymphocyte immunotherapy is a common treatment for RM patients but the outcome has not been consistent. Therefore, combined therapy with other immunosuppressive drugs such as 1 a, 25-dihydroxy-vitamin-D3 (vitamin D3) may improve the outcome. Objectives: To investigate the effect of vitamin D3 on the balance of two essential T cells subsets, T helper (Th) 17 and T regulatory (Treg) cells, which contribute to the immune tolerance during pregnancy. Methods: The expression levels of CD4 and forkhead box protein 3 (FOXP3) in Treg cells, and the expression levels of CD4 and IL- 17 in Th17 cells, were evaluated pre- and 3 months post-immunotherapy in RM patients treated with a combination of paternal lymphocytes and vitamin D3 compared with RM patients receiving lymphocyte immunotherapy alone. Results: Vitamin D3 therapy decreased the frequency of Th17 cells in addition to reducing the Th17/Treg ratio in peripheral blood of RM patients compared with the control group (p <0.05). Conclusion: Considering that RM patients have a higher Th17/Treg ratio in peripheral blood, vitamin D3 may be a candidate therapeutic approach in this disease.}, keywords = {Paternal Lymphocyte Therapy,Recurrent Miscarriage,Regulatory T,Cell,T Helper 17,Vitamin D3}, url = {https://iji.sums.ac.ir/article_16754.html}, eprint = {https://iji.sums.ac.ir/article_16754_cca2542cff564277f9130dda82b85b9e.pdf} } @article { author = {Li, Linge and Hu, Bin and Feng, Juan and Zhang, Yu and Shou, Xi and Tian, Yu and Jiang, Chunrong and Zhang, Hua}, title = {H2-EB1 Molecule Alleviates Allergic Rhinitis Symptoms of H2-Eb1 Knockout Mice}, journal = {Iranian Journal of Immunology}, volume = {12}, number = {4}, pages = {263-273}, year = {2015}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {}, abstract = {Background:   H2-EB1 molecule which is the homolog of Human HLA-DRB1 is proposed to be associated with allergic rhinitis (AR). Construction of   H2-Eb1 knockout animal models provides a tool to elucidate the role of H2-EB1 and AR pathogenesis. Objective:   To establish the H2-Eb1 knockout model and investigate the H2-EB1 functions in   H2-Eb1 knockout mice as a model of AR. Methods: The Cre/LoxP system and ES gene knockout technology were applied to create heterozygous   H2-Eb1 (+/-) knockout mice and their offspring of knockout homozygous(-/-), heterozygous (+/-) and wild type (+/+)   H2-Eb1 mice. After identification, offspring of heterozygous (+/-) and homozygous (-/-)   H2-Eb1 knockout mice were randomly selected to establish AR models to demonstrate the role of   H2-Eb1 in AR pathogenesis. Results: The H2-Eb1 knockout mice model was successfully established. The reproduction and feeding of the homozygous (   -/-) H2-Eb1 knockout mice were successful. Compared with the control group, the serum OVA-IgE and IL-4 levels significantly increased, while IFN-γ levels significantly dropped (p<0.05) in the experimental groups. For the two experimental groups, the homozygous (   -/-) mice group had lower serum OVA-IgE and IL-4 levels, and higher IFN-γ levels than their heterozygous (+/-) counterparts (p<0.05), concomitant with slighter allergic symptoms (gentle behavior and less eosinophils in nasal mucosa).   Conclusion: Our study demonstrated that knockout of H2-Eb1 gene could alleviate mouse AR Symptoms, indicating   H2-Eb1 may play an important role in regulating Th1/Th2 balance during the pathogenesis of AR.}, keywords = {H2-Eb1,Allergic Rhinitis,Knockout,Th1,Th2}, url = {https://iji.sums.ac.ir/article_16755.html}, eprint = {https://iji.sums.ac.ir/article_16755_bf98235bce7d127cd11a84d0dbfad677.pdf} } @article { author = {Mehravaran, Ahmad and Jaafari, Mahmoud Reza and Jalali, Seyed Amir and Khamesipour, Ali and Tafaghodi, Mohsen and Hojatizade, Mansure and Abbasi, Azam and Badiee, Ali}, title = {Cationic Immune Stimulating Complexes Containing Soluble Leishmania Antigens: Preparation, Characterization and in Vivo Immune Response Evaluation}, journal = {Iranian Journal of Immunology}, volume = {12}, number = {4}, pages = {274-287}, year = {2015}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {}, abstract = {Background: Cationic immune stimulating complexes (PLUSCOMs) are particulate antigen delivery systems. PLUSCOMs consist of cationic immunostimulatory complexes (ISCOMs) derivatives and are able to elicit in vivo T cell responses against an antigen. Objective: To evaluate the effects of PLUSCOMs containing Leishmaniamajor antigens (SLA) on the type of immune response generated in the murine model of leishmaniasis. Methods: PLUSCOMs consisting of 1, 2-dioleoyl-3- trimethylammonium-propane (DOTAP) were used as antigen delivery system/immunoadjuvants for soluble SLA. BALB/c mice were immunized subcutaneously, three times in 2-week intervals. Footpads swellings at the site of challenge and parasite loads were assessed as a measure of protection. The immune responses were also evaluated by determination of IgG subclasses and the level of IFN- γ and IL-4 in cultured splenocytes. Results: There was no significant difference (p<0.05) between the sizes of lesions in mice immunized with different formulations. Also, there was no significant difference in the number of parasites in the footpad or spleen of all groups compared with the control group. The highest level of IFN- γ secretion was observed in the splenocytes of mice immunized with PLUSCOM/SLA (p<0.001) and lower amounts of IL-4 was observed in PLUSCOM group (p<0.001) as compared to negative control. Conclusion: Our results indicated that SLA in different formulations generated an immune response with mixed Th1/Th2 response that was not protective enough despite the activation of CD4 + T cells with secreting IFN-γ in groups which received PLUSCOM with antigen.}, keywords = {Leishmania Major,Nanoparticle,PLUSCOM,Vaccine}, url = {https://iji.sums.ac.ir/article_16756.html}, eprint = {https://iji.sums.ac.ir/article_16756_a19544af098ebecf6aedef1c607c0d7b.pdf} } @article { author = {Jafarzadeh, Abdollah and Azizi, Sayyed-Vahab and Nemati, Maryam and Khoramdel-Azad, Hossain and Shamsizadeh, Ali and Ayoobi, Fatemeh and Taghipour, Zahra and Hassan, Zuhair-Mohammad}, title = {Ginger Extract Reduces the Expression of IL-17 and IL-23 in the Seraand Central Nervous System of EAEMice}, journal = {Iranian Journal of Immunology}, volume = {12}, number = {4}, pages = {288-301}, year = {2015}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {}, abstract = {Background: IL-17/IL-23 axis plays an important role in the pathogenesis of several autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). The immunomodulatory properties of ginger are reported in previous studies. Objective: To evaluate the effects of ginger extract on the expression of IL-17 and IL-23 in a model of EAE. Methods: EAE was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein and then treated with PBS or ginger extracts, from day +3 to +30. At day 31, mice were scarificed and the expression of IL-17 and IL-23 mRNA in spinal cord were determined by using real time-PCR. The serum levels of cytokines were measured by ELISA. Results: The mRNA expression of IL-17, IL-23 P19 and IL-23 P40 in CNS and serum levels of IL- 17 and IL-23 were significantly higher in PBS-treated EAE mice than non-EAE group (p<0.003, p<0.001, p<0.001, p<0.05 and p<0.01, respectively). In 200 mg/kg gingertreated EAE mice the mRNA expression of IL-17, P19 and P40 in CNS and serum IL- 23 levels were significantly decreased as compared to PBS-treated EAE mice (p<0.05, p<0.001, p<0.001 and p<0.05, respectively). Moreover, 300 mg/kg ginger-treated EAE group had significantly lower expression of IL-17, P19 and P40 in CNS and lower serum IL-17 and IL-23 levels than PBS-treated EAE group (p<0.02, p<0.001, p<0.001, p<0.03 and p<0.004, respectively). Conclusion: Ginger extract reduces the expression of IL-17 and IL-23 in EAE mice. The therapeutic potential of ginger for treatment of MS could be considered in further studies.}, keywords = {Experimental Autoimmune Encephalomyelitis,Ginger,IL-17,IL-23}, url = {https://iji.sums.ac.ir/article_16757.html}, eprint = {https://iji.sums.ac.ir/article_16757_bb1d1b4d9b78c8f85fe4a55482f0115c.pdf} } @article { author = {Rahmanian, Abdolkarim and Mohebali, Navideh and Haghnegahdar, Ali and Kamali Sarvestani, Eskandar and Razmkon, Ali and Kivelev, Juri and Baghban, Fahim}, title = {Serum Levels of Monocyte Chemoattractant Protein-1 Correlate with Poor Clinical Grades in Cerebral Aneurysms}, journal = {Iranian Journal of Immunology}, volume = {12}, number = {4}, pages = {302-310}, year = {2015}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {}, abstract = {Background : Ruptured cerebral aneurysms (ICAs) are the most common non-traumatic cause of subarachnoid hemorrhage (SAH) that is associated with life threatening complications such as Vasospasm, Infarction, and Hydrocephalus (HCP). The active participation of macrophage/monocyte-mediated inflammatory response in the pathogenesis of cerebral aneurysm as labeled with Monocyte ChemoattractantProtein-1 (MCP-1) is suggested. Objective: To measure the serum level of MCP-1 in ruptured CAs in different time intervals . Methods: We measured the serum levels of MCP-1 in SAH patients who had CAs and compared it with that of MCP-1 in two control groups: including patients with SAH without CAs, and the normal population of blood donors. We also measured the MCP-1 levels in patients with CAs one week afterward to evaluate the effect of treatment. Serum level of MCP-1 was measured by a commercial ELISA assay. Results: Mean serum MCP-1 level in patients with SAH and CAs was 188.2168 Pg/ml and 331.3982 Pg/ml in the normal population. There was no statistically significant difference between serum levels of MCP-1 on the first (mean=188.2168 Pg/ml) and 7 th days after SAH onset (mean=171.8450 Pg/ml) (p=0.739). Serum level of MCP-1 increased significantly as Glasgow Coma Scale decreased (p=0.078) and Hunt and Hess score increased (p=0.089). Conclusion: Our results did not show an increasing MCP-1 serum level in patients with aneurysmal SAH. There was a relationship between poor clinical grade and MCP-1 levels in patients with CAs. MCP-1 may be a local inflammatory marker for cerebral aneurysms without systemic manifestation.}, keywords = {Intracranial Aneurysm,Level,Monocyte Chemoatractic Protein 1,serum}, url = {https://iji.sums.ac.ir/article_16758.html}, eprint = {https://iji.sums.ac.ir/article_16758_7f8968744067617abe9cb5c4ddbf5ae1.pdf} } @article { author = {Jamshidian, Azam and Kazemi, Mohammad and Shaygannejad, Vahid and Salehi, Mansoor}, title = {The Effect of Plasma Exchange on the Expression of FOXP3 and RORC2 in Relapsed Multiple Sclerosis Patients}, journal = {Iranian Journal of Immunology}, volume = {12}, number = {4}, pages = {311-318}, year = {2015}, publisher = {Shiraz Institute for Cancer Research}, issn = {1735-1383}, eissn = {1735-367X}, doi = {}, abstract = {Background: Lack of sufficient information on the mechanism of plasma exchange (PE) therapy in multiple sclerosis (MS), has limited this treatment to individual patients with severe relapses who have been refractory to other treatments. This is while PE is used very successfully as a first-line standard treatment in many other neuro-immune disorders. Recent data suggest that Treg/Th17 counterbalance may indicate the boundaries between promotion and regulation of inflammatory responses in MS and Treg/Th17 ratio may be useful as a marker for monitoring the efficiency of MS therapies. Objective: To evaluate the effect of PE on the frequency and ratio of Treg/Th17 cells through concomitant measurement of the expression levels of Treg and Th17 lineage specific transcription factors, FOXP3 and RORC2, respectively. Methods: Peripheral blood mononuclear cells of 8 relapsed MS patients were obtained before and after a complete course of PE therapy and the FOXP3 and RORC2 mRNA levels were assayed using real-time PCR approach. Results: No significant change in the expression levels of individual transcription factors existed, but a significant increase in FOXP3/RORC2 ratio (p=0.036) was observed. Conclusions: Our results suggest that PE therapy influences Treg/Th17 ratio and this maybe a mechanism by which this procedure exerts its improving effects in MS disease.}, keywords = {Multiple Sclerosis,Plasma Exchange,Th17,Treg}, url = {https://iji.sums.ac.ir/article_16759.html}, eprint = {https://iji.sums.ac.ir/article_16759_b6e3bd186912b195c1001a1dbe461177.pdf} }