Dominant immune cells in pregnancy and pregnancy complications: T helper cells (TH1/TH2, TH17/Treg cells), NK cells, MDSCs, and the immune checkpoints.

Pregnancy problems including recurrent pregnancy loss, repeated implantation failure and pre-eclampsia  are common problems in the reproductive ages. Different reasons such as genetic, immunological, and environmental agents and also infections could develop these complications. In those cases in which the cause of the abortion is diagnosed, the chance of a successful pregnancy is increased by eliminating defective factors. However, in patients with unknown causes, there may be an imbalance in immune cells pattern. As a matter of fact, an inappropriate immune response is often associated with a failed pregnancy. Hence, the focus of treatment is to increase tolerance, not to suppress maternal immune system. These findings are linked to an elevated number of Treg cells and immune checkpoints through normal pregnancy. The present review discusses the balance of myeloid-derived suppressor cells, natural killer cells, T cells, and immune checkpoints, and also targeting them to maintain pregnancy and prevent associated complications.

Evaluation of the immune checkpoint factors in idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN), a single-organ autoimmune disease, is recognized by autoantibodies to podocyte proteins and identified as the most frequent cause of nephrotic syndrome in adults. T cells are important contributors in autoimmunity since they promote B-cell development, antibody production, direct inflammation, and organ tissue cytotoxicity. This study investigated the inhibitory immune checkpoint (ICP) receptors expressed on T lymphocytes and other immune cells. Thus, PBMCs from IMN patients were obtained before treatment, and the levels of ICPs such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte activation gene-3 (LAG-3), and T cell immunoglobulin-3 (TIM-3) were examined at both gene and protein expression using real time PCR and Western blot tests respectively. The results illustrated that gene expression levels of ICPs reduced significantly in comparison to the control which were verified by related fold changes of protein expression sequentially. Our study revealed that CTLA-4, PD-1, TIM-3, and LAG-3 expression is impaired in IMN patients before treatment which could be a potential target for therapy.

Observation of increased levels of autophagy-related genes and proteins in women with preeclampsia: a clinical study.

BACKGROUND: Preeclampsia is a type of pregnancy-related disease that is not fully understood underlying mechanisms of it till now. Reported results from autophagy-related studies in PE show some controversial roles of this mechanism in PE development and progression. In this study, we aimed to evaluate the autophagy process in preeclampsia women. MATERIALS AND METHODS: Peripheral blood was taken from 50 preeclampsia women and 50 healthy pregnant women. After PBMC isolation, Total RNA and total protein were extracted from PBMCs to cDNA synthesis and real-time PCR and western blotting, respectively. Atg5, Atg7, beclin1, LC3B, FOXO1, FOXO3a, FOXO4, and FOXO6 genes were evaluated using real-time PCR. Atg5, beclin1, LC3B, and FOXO1 expression at the protein level was evaluated by the western blot technique. RESULTS: Real-time PCR results showed an increased expression of Atg5, Atg7, beclin1, LC3B, FOXO1, FOXO3a, FOXO4, and FOXO6 genes in PE patients compared to the healthy pregnant women and also in LOPE patients in comparison with EOPE cases. Western blotting results revealed higher expression of Atg5, beclin1, LC3B, and FOXO1 proteins in PE women compared to healthy pregnant group and in LOPE patients in comparison with EOPE cases. Our findings revealed a positive correlation between proteinuria and protein levels of Atg5, beclin1, LC3B, and FOXO1 in LOPE patients. CONCLUSION: Our investigation showed an elevated activation of autophagy in PE women in comparison with healthy pregnant women which is in controversy with some other studies. More targeted and comprehensive studies regarding the relationship of autophagy in pre-eclamptic women are needed.

Evaluation of T helper17 as skeletal homeostasis factor in peripheral blood mononuclear cells and T helper cells of end-stage renal disease cases with impaired parathyroid hormone.

BACKGROUND: Chronic renal failure is mainly connected with high and low parathyroid hormone (PTH) levels and immunological impairments. The present study aimed to evaluate T helper 17 (Th17) cells as a crucial modulator of the immune system and skeletal homeostasis in hemodialysis patients with impaired intact PTH (iPTH). METHODS: In this research, blood samples were taken from ESRD patients with high (> 300 pg/mL), normal (150-300 pg/mL), and low (< 150 pg/mL) serum intact parathyroid hormone (iPTH( levels (n = 30 in each group). The frequency of Th17 (CD4+ IL17+) cells was evaluated by flow cytometry in each group. The expression levels of Th17 cell-related master transcription factors, cytokines in peripheral blood mononuclear cells (PBMC), and Th cells, and the level of the mentioned cytokines were determined in the supernatant of PBMCs. RESULTS: The number of Th17 cells remarkably increased in subjects with high iPTH against low and normal iPTH. Also, RORÉ£t and STAT3 levels were significantly higher in high iPTH ESRD patients than in other groups in the expression of mRNA and protein levels. These findings are confirmed by evaluating the IL-17 and IL-23 in the supernatant of cultured PBMCs and isolated Th cells. CONCLUSION: Our findings indicated that increased serum PTH levels in hemodialysis cases may be involved in increasing the differentiation of CD4 + cells to Th17 cells in PBMC.

The effect of an anti-inflammatory in comparison with a low caloric diet on physical and mental health in overweight and obese women with knee osteoarthritis: a randomized clinical trial.

PURPOSE: To evaluate the effect of an anti-inflammatory compared to a low-calorie diet on the physical and mental health of patients with knee OA. METHODS: In this randomized parallel clinical trial, participants were selected among overweight and obese women aged 40 years or older with mild to moderate OA. Sixty women with a ratio of 1:1 were randomly assigned to receive either low-calorie or anti-inflammatory accompanied by a low-calorie diet for two months. The dietary intake and weight of participants were measured. Study variables were assessed using the Western Ontario and McMaster Index (WOMAC), visual analog pain scale (VAS), Beck Depression Inventory (BDI-II), Beck Anxiety Inventory (BAI-I), and the Short Form 36 Health Survey Questionnaire (SF-36) to indicate the quality of life (QoL). RESULTS: There was no statistically significant difference between the two groups in demographic and baseline variables except for the emotional well-being subscale of QoL. There was significant difference in anti-inflammatory compared to low-calorie diet in terms of weight (MD (95% CI): - 4.02 kg (- 6.77 to - 1.28); p = 0.005), VAS (MD (95% CI): - 0.97 (- 1.53 to - 0.41); p = 0.001), WOMAC-total score (MD (95% CI): - 9.91 (- 15.05 to - 4.78); p < 0.001), WOMAC-pain subscale (MD (95% CI): - 3.30 (- 5.30 to - 1.29); p = 0.002), WOMAC-physical function (MD(95% CI): - 5.48 (- 9.41 to - 1.53); p = 0.007), depression (p = 0.003), anxiety (p = 0.011), QoL-physical functioning (0.041), and QoL-pain (0.010) after the intervention. CONCLUSION: An anti-inflammatory accompanied by a low-calorie diet resulted in greater weight loss and greater improvement in pain intensity, functional status, depression, anxiety, and some dimension of QoL in overweight and obese women with knee OA compared to the low-calorie diet. Trial registration number and date of registration: IRCT201610220030424N2; 2018-04-23.

Platelet lysate and tendon healing: comparative analysis of autologous frozen-thawed PRP and ketorolac tromethamine in the treatment of patients with rotator cuff tendinopathy.

Platelet-rich blood derivatives are being nowadays increasingly used in the treatment of tendon-related pathologies as a rich source of growth factors. We sought to ascertain if local application of platelet lysate (PL) to augment rotator cuff repair ameliorates patient outcomes compared to ketorolac tromethamine treated group. A total of forty patients, with clinical diagnosis of Rotator Cuff Tendinopathy were randomized to receive sub acromial injections of PL every week for a total of 3 injections and two injection of ketorolac tromethamine once every two weeks. Subjective assessments included VAS, SPADI and shoulder range of motion were assessed at baseline and at 1 and 6 months after injection. Taking both control and PL groups, it was vividly seen that the outcomes were identical at the initial state, as well as the short-term one; whereas, when considering the 6-month period, there is a seemingly remarkable superiority in PL group in all parameters.

Stem cells technology as a platform for generating reproductive system organoids and treatment of infertility-related diseases.

In recent years, stem cells have known as a helpful biological tool for the accurate diagnosis, treatment and recognition of diseases. Using stem cells as biomarkers have presented high potential in the early detection of many diseases. Another advancement in stem cell technology includes stem cell derived organoids model that could be a promising platform for diagnosis and modeling different diseases. Furthermore, therapeutic capabilities of stem cell therapy have increased hope in the face of different disability managements. All of these technologies are also widely used in reproductive related diseases especially in today's world that many couples encounter infertility problems. However, with the aid of numerous improvements in the treatment of infertility, over 80% of couples who dreamed of having children could now have children. Due to the fact that infertility has many negative effects on personal and social lives of young couples, many researchers have focused on the treatment of male and female reproductive system abnormalities with different types of stem cells, including embryonic stem cells, bone marrow mesenchymal stem cells (MSCs), and umbilical cord-derived MSCs. Also, design and formation of reproductive system organoids provide a fascinating window into disease modeling, drug screening, personalized therapy, and regeneration medicine. Utilizing these techniques to study, model and treat the infertility-related diseases has drawn attention of many scientists. This review explains different applications of stem cells in generating reproductive system organoids and stem cell-based therapies for male and female infertility related diseases treatment.

SARS-CoV-2 vaccines: A double-edged sword throughout rapid evolution of COVID-19.

After more than 2 years of the coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2, several questions have remained unanswered that affected our daily lives. Although substantial vaccine development could resist this challenge, emerging new variants in different countries could be considered as potent concerns regarding the adverse effects of reinfection or postvaccination. Precisely, these concerns address some significant and probable outcomes in vaccinated or reinfected models, followed by some virus challenges, such as antibody-dependent enhancement and cytokine storm. Therefore, the importance of evaluating the effectiveness of neutralizing antibodies (nAbs) elicited by vaccination and the rise of new variants must be addressed.

Autologous conditioned serum for degenerative diseases and prospects.

Autologous conditioned serum (ACS) is a blood-derived product that is prepared by the incubation of whole blood with medical-grade glass beads, resulting in serum enrichment in interleukin-1 receptor antagonist (IL-1Ra), anti-inflammatory cytokines (IL-4, IL-10, and IL-13), and high concentrations of growth factors. ACS has shown qualitatively and quantitatively better therapeutic effects than most established pharmacological treatments and surgery for joint diseases given its ability to both target the inflammatory cascade to decrease cartilage destruction as well as improve endogenous repair mechanisms. ACS application is simple and safe with limited adverse effects. This article reviews the role of ACS in degenerative joint disease, in addition to other inflammatory and autoimmune diseases, given its regenerative and immune-modulating properties.

The emerging role of microRNA in regulating the mTOR signaling pathway in immune and inflammatory responses.

The mechanistic/mammalian target of rapamycin (mTOR) is considered to be an atypical protein kinase that plays a critical role in integrating different cellular and environmental inputs in the form of growth factors, nutrients and energy and, subsequently, in regulating different cellular events, including cell metabolism, survival, homeostasis, growth and cellular differentiation. Immunologically, mTOR is a critical regulator of immune function through integrating numerous signals from the immune microenvironment, which coordinates the functions of immune cells and T cell fate decisions. The crucial role of mTOR in immune responses has been lately even more appreciated. MicroRNAs (miRNAs) are endogenous, small, noncoding single-stranded RNAs that act as molecular regulators involved in multiple processes during immune cells development, homeostasis, activation and effector polarization. Several studies have recently indicated that a range of miRNAs are involved in regulating the phosphoinositide 3-kinase/protein kinase B/mTOR (PI3K/AKT/mTOR) signaling pathway by targeting multiple components of this signaling pathway and modulating the expression and function of these targets. Current evidence has revealed the interplay between miRNAs and the mTOR pathway circuits in various immune cell types. The expression of individual miRNA can affect the function of mTOR signaling to determine the cell fate decisions in immune responses through coordinating immune signaling and cell metabolism. Dysregulation of the mTOR pathway/miRNAs crosstalk has been reported in cancers and various immune-related diseases. Thus, expression profiles of dysregulated miRNAs could influence the mTOR pathway, resulting in the promotion of aberrant immunity. This review summarizes the latest information regarding the reciprocal role of the mTOR signaling pathway and miRNAs in orchestrating immune responses.

Nanoparticles and cancer therapy: Perspectives for application of nanoparticles in the treatment of cancers.

Rapid growth in nanotechnology toward the development of nanomedicine agents holds massive promise to improve therapeutic approaches against cancer. Nanomedicine products represent an opportunity to achieve sophisticated targeting strategies and multifunctionality. Nowadays, nanoparticles (NPs) have multiple applications in different branches of science. In recent years, NPs have repetitively been reported to play a significant role in modern medicine. They have been analyzed for different clinical applications, such as drug carriers, gene delivery to tumors, and contrast agents in imaging. A wide range of nanomaterials based on organic, inorganic, lipid, or glycan compounds, as well as on synthetic polymers has been utilized for the development and improvement of new cancer therapeutics. In this study, we discuss the role of NPs in treating cancer among different drug delivery methods for cancer therapy.

The effects of nanocurcumin on Treg cell responses and treatment of ankylosing spondylitis patients: A randomized, double-blind, placebo-controlled clinical trial.

AIM: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with increased bone mass in the main sites of inflammation. Regulatory T (Treg) cells have been reported to involve in pathology of AS. This study designed at investigating the effects of nanocurcumin on Treg cell responses in peripheral blood (PB) of AS patients. METHODS: Test group including 12 AS patients received nanocurcumin daily for 4 months and control group including 12 patients received placebo. The frequency of Treg was measured by flow cytometry. The expression levels of FoxP3 and several associated microRNAs (miRNAs; miR-27, miR-17, and miR-146a) and cytokines including Interleukin-10 (IL-10), TGF-ß, and IL-6 were assessed by real-time polymerase chain reaction. Furthermore, enzyme-linked immunosorbent assay was done to determine the secretion levels of cytokines. RESULTS: After treatment with nanocurcumin the frequency of Treg cells in AS patients increased significantly. The RT-PCR data indicated that the expression of miR-17 and miR-27 were significantly decreased following nanocurcumin treatment while miR-146a and FoxP3 were significantly increased. Moreover, nanocurcumin-treated group had high levels of IL-10 and TGF-ß and low levels of IL-6 production than control group. CONCLUSION: The findings suggested that dysregulation of Treg cells in PB influences the AS development and nanocurcumin therapy could regulate the Treg cells, and so could be useful in the treatment of AS and may be other autoimmune diseases. This study is registered with IRCT.ir, number IRCT2017052927520N7.

Prospects for the application of growth factors in wound healing.

As the largest organ of the body, human skin is multifunctional and enjoys two layers, the epidermis and the dermis, the separation of which is performed by a basement membrane zone. Skin protects the body against mechanical forces and infections. Skin wounds represent large and growing challenges to the healthcare systems globally. Skin wound healing, as a protective shield for the body against the external environment, includes interactions among cell types, the neurovascular system, cytokines, and matrix remodeling. Growth factors (GFs) affect the microenvironment of the wound, and cause rises in cell differentiation, proliferation, and migration. Administrating exogenous GFs has revealed potential in enhancing wound healing outcomes. The use of human GFs in the field of wound healing is becoming gradually more interesting, because of the low-invasive techniques required for their use. Reviewed here are the literatures on the healing of skin wounds with emphasize on the role of GFs and their future prospects, containing profits, and probable long-standing side effects accompanied with their use.

Biosensors: A novel approach to and recent discovery in detection of cytokines.

Cytokines in tissues and physiological fluids can function as potentially suitable biomarkers. Cytokines are involved in stimulating different body responses including inflammatory response to external pathogens, regulating cell-to-cell communication, and maintaining tissue homeostasis. Consequently, cytokines are extensively used to monitor and predict disease progression and to track the outcome of patient treatment. The critical diagnosis of cytokine and chemokine biomarkers has been the focus of attention and it has been continuously directing the trajectory of related research to developing a novel sensing platform. Given the major challenges and constraints of the older identification methods including their high costs, low sensitivity, and high specificity, the development of biosensor technology as a simple and inexpensive tool with high sensitivity is quite attractive and interesting. The fundamental aim of this study is to present the state-of-the-art biosensor systems in order to detect different types of cytokines and to emphasize the role of these systems in the prevention, monitoring, and treatment of various cytokine-associated diseases.

Osteosarcoma: A comprehensive review of management and treatment strategies.

Osteosarcoma, a bone cancer usually seen in children and young adults, is generally a high-grade malignancy presented by extreme metastases to the lungs. Osteosarcoma has a tendency for appearing in bones with rapid growth rate. The etiology of osteosarcoma is multifaceted and poorly understood. A molecular consideration of this disease will lead to a directed tumor treatment. The present treatment for osteosarcoma comprises of an arrangement of systemic chemotherapy and wide surgical resection. Survival rate is increased by the progress of destructive systemic chemotherapies. So, the development of new treatment approaches for metastatic osteosarcoma is essential. Immunomodulation has been used in clinical settings. Through targeting surface antigens expressed on tumor cells, particular antibodies and exploitation of cellular immunotherapy against sarcomas have been confirmed to be effective as cancer therapeutics. In this article, we have reviewed epidemiology, etiology, pathogenesis, diagnosis, and treatment of osteosarcoma and we have focused on different methods of immunotherapy including vaccines, cell-based immunotherapy, cytokines, and monoclonal antibodies.

mTOR Signaling pathway as a master regulator of memory CD8+ T-cells, Th17, and NK cells development and their functional properties.

The mammalian target of rapamycin (mTOR) is a member of the evolutionary phosphatidylinositol kinase-related kinases (PIKKs). mTOR plays a pivotal role in the regulation of diverse aspects of cellular physiology such as body metabolism, cell growth, protein synthesis, cell size, autophagy, and cell differentiation. Immunologically, mTOR has a fundamental part in controlling and shaping diverse functions of innate and adaptive immune cells, in particular, T-cell subsets differentiation, survival, and metabolic reprogramming to ultimately regulate the fate of diverse immune cell types. Researchers report that rapamycin, a selective mTOR inhibitor, and immunosuppressive agent, has surprising immunostimulatory effects on inducing both quantitative and qualitative aspects of virus-specific memory CD8+ T-cells differentiation and homeostasis in a T-cell-intrinsic manner. The mTOR signaling pathway also plays a critical role in dictating the outcome of regulatory T cells (Treg), T helper 17 (Th17) cells, and natural killer (NK) cells proliferation and maturation, as well as the effector functions and cytotoxic properties of NK cells. Manipulation of mTOR activity is a critical therapeutic approach for pharmacological agents that seek to inhibit mTOR. This approach should enhance specific memory CD8 + T-cells responses and induce fully functional effector properties of NK cells to provoke their antitumor and antiviral activities.

Prospect of mesenchymal stem cells in therapy of osteoporosis: A review.

Osteoporosis is a systemic skeletal disease associated with reduced bone strong point that results in raised fracture risk, with decreased bone strength, leading to reduced bone mineral density and poor bone quality. It is the most common in older females but some men are also at high risk. Although considered as a predictable result of aging, it is can be avoidable and treatable. The existing treatment of osteoporosis mainly contains antiresorptive and anabolic agents. In spite of these improvements, concerns around unusual side-effects of antiresorptive drugs, and the lack of perfect confirmation in maintenance of their long-standing effectiveness is bring about many patients not receiving these drugs. Over the years, the stem cell-based therapy has attained substantial clinical consideration because of its potential to treat numerous diseases. The stem cell therapy has been recommended as a probable therapeutic approach for patients with osteoporosis. Even though the concept of stem cell-based therapy for osteoporosis has caught substantial attention, no clinical trial has been published on humans. The cell studies based on osteoporosis are primarily focused on osteoclastic activity and bone resorption procedures. Earlier, it was on osteoblastogenesis and in recent times, on the differentiation probable of mesenchymal stem cells. In this review, we have summarized the therapeutic role of stem cell-based strategy in osteoporosis.

Disturbed Th17/Treg balance, cytokines, and miRNAs in peripheral blood of patients with Behcet's disease.

Impaired inflammatory immune cells have been implicated in the pathogenesis of Behcet's disease (BD). In the current study, we aimed to evaluate the frequency of T helper (Th) 17 and regulatory T (Treg) cells, cytokine secretion, the expression of transcription factors related to Th17 and Treg cells, and microRNAs (miRNAs) targeting these transcription factors in BD patients. Blood samples from 47 BD patients and 58 healthy subjects were drawn, and the peripheral blood mononuclear cells (PBMCs) were separated and isolated. The frequency of Th17 and Treg cells was assessed using flow cytometry. Transcription factors related to these cells and miRNAs targeting these transcription factors were quantified using real-time polymerase chain reaction. Finally, the levels of associated cytokines were measured using enzyme-linked immunosorbent assay. A significant reduction in the percentage of Treg cell frequency and the levels of interleukin (IL)-10 and forkhead box P3 messenger RNA (mRNA) expressions were observed. The proportion of Th17 cells was notably increased, which was accompanied by a increased levels of IL-17, IL-23, and retinoic acid-related orphan receptor ɣ (RORɣt) mRNA expressions in BD patients. The level of Th17-associated cytokines in the supernatant was found to be elevated in BD patients. T-cell-associated miRNA expression levels, miR-25, miR-106b, miR-326, and miR-93 were significantly upregulated, while miR-146a and miR-155 levels were lower in PBMCs of patients with BD when compared with the controls. The increase in the proportion of Th17 cells alongside the decrease in Treg cells are possibly the involving factors in the pathogenesis of BD. Therefore, the evaluation of immune cells and related miRNA profile may serve as both prognostic biomarker and therapeutic approach in treating patients with BD.

The imbalance of Th17/Treg axis involved in the pathogenesis of preeclampsia.

PROBLEM: Inappropriate activation of the immune system, particularly the imbalance of T-helper type 17 (Th17)/regulatory T (Treg) cells is thought to play considerable roles in preeclampsia (PE). To investigate the probable effects of the adaptive immune system in the pathophysiology of PE, we analyzed the dynamic changes of Th17/Treg cells, cytokines profile, and transcription pattern of Th17/Treg-related genes and microRNAs (miRNAs) in 50 women suffering from PE in comparison with 50 healthy pregnant women. METHODS: Expressions of cytokines, specific transcription factors, and related miRNAs were measured by real-time polymerase chain reaction (PCR). Enzyme-linked immunosorbent assay (ELISA) was used to test the interleukin (IL)-17, IL-23, IL-6, and IL-10 and transforming growth factor ß in serum and supernatant of peripheral blood mononuclear cells (PBMCs). The frequency of Th17 and Treg cells were determined by flow cytometry. RESULTS: PE patients exhibited a decreased number of Treg cells (p = 0.006), while Th17 cells were increased ( p = 0.004). Forkhead box P3 and IL-10 mRNA expressions were reduced ( p = 0.0001 and 0.0028, respectively), while expressions of retinoic acid receptor-related orphan nuclear receptor γt, IL-17, IL-23, and IL-6 were enhanced ( p < 0.0001, 0.0018, 0.0014, and 0.027, respectively). ELISA results also showed increased levels of IL-6, IL-17, and IL-23 ( p = 0.022, 0.0005, 0.0081, respectively), and decreased levels of IL-10 in the supernatant of PBMCs of PE patients compared with control group ( p = 0.0011). There was significant upregulation of miR-106b and miR-326 ( p = 0.0048 and 0.028, respectively) in PE patients in comparison with the control group. CONCLUSIONS: These findings suggest that imbalance of Th17/Treg cells, regulated possibly via microRNAs, may be involved in the pathogenesis of PE, emphasizing on the importance of these cells in feto-maternal immune cross-talk.

Cyclosporine A improves pregnancy outcomes in women with recurrent pregnancy loss and elevated Th1/Th2 ratio.

Recurrent pregnancy loss (RPL) is a one of the most common obstetrical complications. Since, the successful pregnancy occurs in T helper 2 (Th2)-dominant situation and since, Th1 type immunity is related to pregnancy failure, we investigated the effects of cyclosporine on Th1 and Th2 cells in RPL women. Totally, 76 RPL patients (38 women as treated group and 38 as control group) were included in this study. Flow cytometry was utilized to analyze the frequency of Th1 and Th2 in blood samples. Also, real-time polymerase chain reaction was carried out to assess the messenger RNA (mRNA) expression of transcription factors and enzyme-linked immunosorbent assay was used to evaluate Th1 and Th2 related cytokines. Significant decrease in Th1 frequency (p = 0.0004), Th1/Th2 ratio (p < 0.0001), T-bet mRNA expression (p < 0.0001), interferon-γ (p = 0.0007), and tumor necrosis factor α (p = 0.0002) secretion level were observed in cyclosporine group. Moreover, significant increase in Th2 frequency (p < 0.0001), mRNA expression of GATA binding protein 3 (p = 0.0001), and interleukin 10 secretion level (p = 0.0027) was also evident in treated group. At the end of the investigation, 31 (81.5%) patients in cyclosporine-treated group had successful childbirth when compared with 16 (42.1%) women in control group (p = 0.0001). Given this, cyclosporine treatment for RPL patients with elevated Th1/Th2 ratio can result in improved pregnancy outcome.