Tumor Associated Mesenchymal Stromal Cells Show Higher Immunosuppressive and Angiogenic Properties Compared to Adipose Derived MSCs
Ladan
Langroudi
Department of Immunology
author
Zuhair Muhammad
Hassan
Department of Immunology
author
Masoud
Soleimani
Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares
University
author
Seyed Mahmoud
Hashemi
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical
Sciences, Tehran, Iran
author
text
article
2015
eng
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.
Iranian Journal of Immunology
Shiraz Institute for Cancer Research
1735-1383
12
v.
4
no.
2015
226
239
https://iji.sums.ac.ir/article_16752_d84d806bc2cd96fa325eb07adc3d33a6.pdf
Altered Suppressor Function of Regulatory T Cells in Type 1 Diabetes
Babak
Aghili
Department of Immunology, School of Medicine
author
Ali Akbar
Amirzargar
Department of Immunology, School of Medicine
author
Asadollah
Rajab
Department of Endocrinology, Iranian Diabetes Association
author
Ali
Rabbani
Growth and
Development Center, Tehran University of Medical Sciences, Children's Medical Center
author
Arya
Sotoudeh
Growth and
Development Center, Tehran University of Medical Sciences, Children's Medical Center
author
Sara
Assadiasl
Department of Immunology, School of Medicine
author
Bagher
Larijani
Endocrinology
and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran
author
Ahmad
Massoud
Department of Immunology, School of Medicine
author
text
article
2015
eng
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.
Iranian Journal of Immunology
Shiraz Institute for Cancer Research
1735-1383
12
v.
4
no.
2015
240
251
https://iji.sums.ac.ir/article_16753_babc63ff6b42a4cd066e054e8cdad6fe.pdf
Altered Th17/Treg Ratio in Recurrent Miscarriage after Treatment with Paternal Lymphocytes and Vitamin D3: a Double- Blind Placebo-Controlled Study
Mitra
Rafiee
Department of Immunology, School of Medicine
author
Marjan
Gharagozloo
Department of Immunology, School of Medicine
author
Ataollah
Ghahiri
Department of Gynecology and Obstetrics, Al-Zahra
University Hospital
author
Ferdous
Mehrabian
Department of Gynecology and Obstetrics, Al-Zahra
University Hospital
author
Mohammad R.
Maracy
Department of Community Medicine, School of Medicine, Isfahan University of
Medical Sciences, Isfahan, Iran
author
Shirin
Kouhpayeh
Department of Immunology, School of Medicine
author
Ina Laura
Pieper
Institute of Life Science, College of Medicine, Swansea University,
Swansea, United Kingdom
author
Abbas
Rezaei
Department of Immunology, School of Medicine
author
text
article
2015
eng
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.
Iranian Journal of Immunology
Shiraz Institute for Cancer Research
1735-1383
12
v.
4
no.
2015
252
262
https://iji.sums.ac.ir/article_16754_cca2542cff564277f9130dda82b85b9e.pdf
H2-EB1 Molecule Alleviates Allergic Rhinitis Symptoms of H2-Eb1 Knockout Mice
Linge
Li
Department of Otorhinolaryngology, the First Affiliated Hospital, Xinjiang Medical University, Urumqi,
Xinjiang, China
author
Bin
Hu
Department of Otorhinolaryngology, the First Affiliated Hospital, Xinjiang Medical University, Urumqi,
Xinjiang, China
author
Juan
Feng
Department of Otorhinolaryngology, the First Affiliated Hospital, Xinjiang Medical University, Urumqi,
Xinjiang, China
author
Yu
Zhang
Department of Otorhinolaryngology, the First Affiliated Hospital, Xinjiang Medical University, Urumqi,
Xinjiang, China
author
Xi
Shou
Department of Otorhinolaryngology, the First Affiliated Hospital, Xinjiang Medical University, Urumqi,
Xinjiang, China
author
Yu
Tian
Department of Otorhinolaryngology, the First Affiliated Hospital, Xinjiang Medical University, Urumqi,
Xinjiang, China
author
Chunrong
Jiang
Department of Otorhinolaryngology, the First Affiliated Hospital, Xinjiang Medical University, Urumqi,
Xinjiang, China
author
Hua
Zhang
Department of Otorhinolaryngology, the First Affiliated Hospital, Xinjiang Medical University, Urumqi,
Xinjiang, China
author
text
article
2015
eng
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.
Iranian Journal of Immunology
Shiraz Institute for Cancer Research
1735-1383
12
v.
4
no.
2015
263
273
https://iji.sums.ac.ir/article_16755_bf98235bce7d127cd11a84d0dbfad677.pdf
Cationic Immune Stimulating Complexes Containing Soluble Leishmania Antigens: Preparation, Characterization and in Vivo Immune Response Evaluation
Ahmad
Mehravaran
Nanotechnology Research Center, School of Pharmacy
author
Mahmoud Reza
Jaafari
Nanotechnology Research Center, School of
Pharmacy, Mashhad University of Medical Sciences, Mashhad
author
Seyed Amir
Jalali
Department of Immunology, Medical
School, Shahid Beheshti University of Medical Sciences
author
Ali
Khamesipour
Center for Research and Training in Skin
Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran
author
Mohsen
Tafaghodi
Nanotechnology Research Center, School of Pharmacy
author
Mansure
Hojatizade
Nanotechnology Research Center, School of Pharmacy
author
Azam
Abbasi
Nanotechnology Research Center, School of Pharmacy
author
Ali
Badiee
Nanotechnology Research Center, School of Pharmacy
author
text
article
2015
eng
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.
Iranian Journal of Immunology
Shiraz Institute for Cancer Research
1735-1383
12
v.
4
no.
2015
274
287
https://iji.sums.ac.ir/article_16756_a19544af098ebecf6aedef1c607c0d7b.pdf
Ginger Extract Reduces the Expression of IL-17 and IL-23 in the Seraand Central Nervous System of EAEMice
Abdollah
Jafarzadeh
Department of Immunology, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan
author
Sayyed-Vahab
Azizi
Department of Immunology, Medical School,
Kerman University of Medical Sciences, Kerman
author
Maryam
Nemati
Neuroscience Research Center, Department of Neurology
author
Hossain
Khoramdel-Azad
Department of Immunology, Medical School,
Kerman University of Medical Sciences, Kerman
author
Ali
Shamsizadeh
Department of Physiology, Medical School
author
Fatemeh
Ayoobi
Department of Physiology, Medical School
author
Zahra
Taghipour
Department of Histology, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan
author
Zuhair-Mohammad
Hassan
Department of Immunology, Medical School, Tarbiat Moddares University, Tehran, Iran
author
text
article
2015
eng
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.
Iranian Journal of Immunology
Shiraz Institute for Cancer Research
1735-1383
12
v.
4
no.
2015
288
301
https://iji.sums.ac.ir/article_16757_bb1d1b4d9b78c8f85fe4a55482f0115c.pdf
Serum Levels of Monocyte Chemoattractant Protein-1 Correlate with Poor Clinical Grades in Cerebral Aneurysms
Abdolkarim
Rahmanian
Department of Neurosurgery
author
Navideh
Mohebali
Department of Neurosurgery
author
Ali
Haghnegahdar
Department of Neurosurgery
author
Eskandar
Kamali Sarvestani
Department of Immunology, Shiraz Medical School, Shiraz University of
Medical Sciences, Shiraz, Iran
author
Ali
Razmkon
Department of Neurosurgery
author
Juri
Kivelev
Department of Neurosurgery, Helsinki University Central Hospital,
Topeliuksenkatu, Finland
author
Fahim
Baghban
Department of Neurosurgery
author
text
article
2015
eng
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.
Iranian Journal of Immunology
Shiraz Institute for Cancer Research
1735-1383
12
v.
4
no.
2015
302
310
https://iji.sums.ac.ir/article_16758_7f8968744067617abe9cb5c4ddbf5ae1.pdf
The Effect of Plasma Exchange on the Expression of FOXP3 and RORC2 in Relapsed Multiple Sclerosis Patients
Azam
Jamshidian
Department of Microbiology and Immunology, School of Medicine, Shahrekord University of Medical
Sciences, Shahrekord
author
Mohammad
Kazemi
Department of Genetic and Molecular Biology
author
Vahid
Shaygannejad
Department of Neurology, School
of Medicine
author
Mansoor
Salehi
Applied Physiology Research Center, Isfahan
University of Medical Sciences, Isfahan, Iran
author
text
article
2015
eng
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.
Iranian Journal of Immunology
Shiraz Institute for Cancer Research
1735-1383
12
v.
4
no.
2015
311
318
https://iji.sums.ac.ir/article_16759_b6e3bd186912b195c1001a1dbe461177.pdf