"Decoding inflammation: glycoprotein a repetition predominant, microRNA-142-3-p, and metastasis associated lung adenocarcinoma transcript 1: as novel inflammatory biomarkers of inflammatory bowel disease".

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic gastrointestinal (GI) condition comprising Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis involves immune system dysregulation, with increased Th (T helper cell)17 cells and reduced regulatory T cell (Treg) differentiation. Transforming growth factor-ß (TGF-ß) secretion from Tregs helps control inflammation, and its production is regulated by glycoprotein-A repetition predominant (GARP) protein along with non-coding RNAs (ncRNAs) like microRNA(miR)-142-3p and metastasis associated lung adenocarcinoma transcript 1 (MALAT1) long non-coding RNAs (LncRNAs). This study analyzed their expression in IBD. METHODS: Blood samples were collected from 44 IBD patients, and 22 healthy controls (HC). RNA extraction and circular DNA (cDNA) synthesis were performed. Real-time polymerase chain reaction (RT-PCR) measured gene expression of GARP, MALAT1, and miR-142-3p. Correlations and group differences were statistically analyzed. RESULTS: Compared to controls, GARP was downregulated while MALAT1 and miR-142-3p were upregulated significantly in IBD group. GARP and MALAT1 expressions positively correlated in controls. MALAT1 and miR-142-3p expressions positively correlated in IBD group. MALAT1 was downregulated in aged HC but upregulated with smoking history across groups. No correlations occurred between gene expression and gender, diet, infections, or disease activity scores. CONCLUSIONS: Dysregulation of GARP, MALAT1, and miR-142-3p likely contributes to inflammation in IBD by reducing TGF-ß. MALAT1 is linked to smoking and age-related changes. These genes have potential as diagnostic markers or therapeutic targets for personalized IBD treatment.

Cytokine and chemokine profiles in women with endometriosis, polycystic ovary syndrome, and unexplained infertility.

Numerous factors (including immunological, congenital, hormonal, and morphological disorders) can lead to infertility. In this regard, 3 specific diseases associated with infertility are discussed in this review study (i.e., polycystic ovary syndrome [PCOS], endometriosis [EMS], and unexplained infertility [UI]). PCOS is a common endocrine disorder characterized by chronic low-grade inflammation, and EMS is a benign disease characterized by the presence of ectopic endometrial tissue. UI refers to couples who are unable to conceive for no known reason. Conception and pregnancy are significantly affected by the immune system; in this regard, chemokines and cytokines play important roles in the regulation of immune responses. Patients with PCOS, EMS, and UI have altered cytokine and chemokine profiles, suggesting that dysregulation of these molecules may contribute to infertility in these conditions. Accordingly, the issue of infertility is addressed in this review study, a condition that affects approximately 16% of couples worldwide.

Increased frequency of CD39+CD73+ regulatory T cells and Deltex-1 gene expression level in kidney transplant recipients with excellent long-term graft function.

BACKGROUND: The ability of regulatory T cells (Tregs) to limit inflammatory responses has been demonstrated. However, different subpopulations of this cell have varying abilities to suppress alloreactive immune responses. The primary goal of this study was to assess the frequency of CD4+FOXP3+CD39+CD73+ Tregs and Deltex-1 gene expression on long-term renal transplant function. METHODS: A total of 49 subjects were divided into 3 groups: (i) the excellent long-term graft function (ELTGF) group, (ii) the chronic graft dysfunction (CGD) group, and (iii) the healthy control (HC) group. Following sample collection, peripheral blood mononuclear cells (PBMCs) were isolated, and the Deltex-1 gene expression level and the frequency of CD4+FOXP3+CD39+CD73+ Tregs were evaluated. RESULTS: The ELTGF group had more CD4+FOXP3+ Tregs than the CGD group, but the difference was not statistically significant (P = 0.07). However, the frequency of CD4+FOXP3+CD39+CD73+ Tregs and the ratio of these cells to total CD4+ lymphocytes significantly increased in the ELTGF group than in the CGD group (P = 0.04 and P = 0.02 respectively). In addition, the expression level of the Deltex-1 gene was significantly lower in the CGD group than in the other 2 groups (P = 0.01 and P = 0.04 respectively). CONCLUSIONS: Given the increased frequency of CD4+FOXP3+CD39+CD73+ Tregs and the expression level of the Deltex-1 gene in the ELTGF group, it appears that these factors probably improved function and long-term survival of the transplanted organ through the suppression of alloreactive responses and reduction of inflammation. In other words, one of the immunological mechanisms involved in the CGD group may be a deficiency in Tregs.

Decreased frequency of regulatory T cells and level of helios gene expression in secondary progressive multiple sclerosis patients: Evidence about the development of multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an aggressive disease characterized by central nervous system (CNS) inflammatory and demyelinating lesions. Tolerance failure is implicated in the development of several autoimmune disorders, including MS. Due to their involvement in maintaining environmental tolerance, regulatory T cells (Tregs) are regarded as efficient immune cells. We examined the frequency of Tregs in this study using CD4/CD25/forkhead box protein P3 (FOXP3)/Helios markers. METHODS: Fifty participants, including 25 patients with secondary progressive MS (SPMS) and 25 healthy controls (HCs), were enrolled in this study, and their demographic characteristics were recorded. Peripheral blood samples ranging from 5 to 6 mL were obtained, and the Ficoll technique was used to extract peripheral blood mononuclear cells (PBMCs). Then, the percentage of CD4+CD25+FOXP3+Helios+ regulatory T lymphocytes was examined by flow cytometry in the study groups. Real-time polymerase chain reaction (PCR) was also used to assess the Helios gene expression level. RESULTS: This study showed that the percentage of Tregs with CD4 and CD25 markers did not reveal a significant difference compared with HCs despite the decrease in SPMS patients (P = 0.6). However, lymphocytes with CD4/CD25/FOXP3/Helios markers were significantly reduced in the patients (P = 0.01). Additionally, SPMS patients had statistically significantly lower Helios gene expression levels (P = 0.002). CONCLUSION: In SPMS patients, a decrease in the frequency of the CD4+CD25+FOXP3+Helios+ Treg population can result in an imbalanced immune system. In other words, one of the immunological mechanisms involved in this disease may be a deficiency in Tregs. Helios gene expression was also decreased in these patients, which may exacerbate functional defects in Tregs.

Vitamin D receptor expression in sperm of males with unexplained infertility.

Background: Vitamin D is associated with numerous disorders, including infertility. Accordingly, the goal of this research was to find out the level of vitamin D and messenger RNA (mRNA) expression of vitamin D receptor (VDR) in the sperm of male subjects with unexplained infertility. Methods: Twenty-four unexplained infertile men as the case group and 22 healthy fertile men as the control group were recruited. Vitamin D levels were evaluated in seminal fluid using enzyme-linked immunosorbent assay (ELISA). Afterwards, the swim-up test was performed to isolate motile sperm cells. From these cells, RNA was extracted, complementary DNA (cDNA) was synthesized, and mRNA expression of the VDR gene was evaluated with quantitative real-time polymerase chain reaction (PCR). Results: A decrease in VDR mRNA expression levels was detected in the case group compared to the control group, but this reduction was not statistically significant (p>0.05). Besides, the level of vitamin D in seminal fluid was not detectable in both groups. Conclusion: The sperm of unexplained infertile men express VDR gene mRNA, although there was no vitamin D in seminal samples. Hence, vitamin D and VDR signaling might not be effective in the etiopathogenesis of unexplained infertility in men.

Increased frequency of activated regulatory T cells in patients with lupus nephritis.

BACKGROUND AND OBJECTIVE: Lupus nephritis (LN) is one of the common manifestations of systemic lupus erythematosus (SLE), affecting the quality of life of patients. Abnormality in the adaptive immune response, such as T cell response, plays the main role in the pathogenesis of SLE and LN. In this study, we aimed to evaluate the role of different subpopulations of regulatory T cells (Tregs) and effector T cells (Teff) in LN patients and compare them with SLE patients. MATERIALS AND METHODS: A total of 48 participants were enrolled in this study and divided into 3 groups: (i) patients with SLE; (ii) patients with LN; and (iii) healthy controls (HCs). The frequencies of CD4+ CD25++ CD45RA- Foxp3hi activated Tregs (aTregs), CD4+ CD25+ CD45RA+ Foxp3lo resting Tregs (rTregs), CD4+ CD25+ CD45RA- Foxp3lo non-Tregs, CD4+ CD25+ Foxp3- Teff, and Tregs were analyzed in all subjects using a flow cytometer. RESULTS: LN patients had a significantly increased frequency of aTregs and Tregs compared with SLE patients (standardized mean difference [SMD] = 0.50; 95% CI [-0.26, 1.25]; p > 0.05 and SMD = 0.60; 95% CI [-0.16, 1.36]; p > 0.05, respectively). Patients with LN had a significantly increased frequency of Teff compared with SLE patients (SMD = 0.49; 95% CI [-0.26, 1.24]; p > 0.05). However, an increased ratio of Tregs/Teff was observed in LN patients compared with SLE patients (SMD = -0.25; 95% CI [-0.97, 0.48]; p > 0.05). CONCLUSION: Patients with LN showed immunoregulatory properties, in which both aTregs and Tregs had increased frequencies.

The association of decreased HLA-G+ immune cell frequencies with critical COVID-19 patients.

INTRODUCTION: COVID-19 (coronavirus disease-2019) is an infectious disease caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Immune dysregulation causes inflammation and massive production of inflammatory mediators that worsen the patients' status. Here, regulatory immune cells may ameliorate inflammation and improve the severity of the disease. MATERIALS AND METHODS: A total of 76 participants were enrolled in this study and divided into 3 groups as follows: patients with moderate/severe COVID-19 (n = 25), patients with critical COVID-19 (n = 26), and healthy controls (n = 25). After blood collection, peripheral blood mononuclear cells (PBMCs) were isolated and stained by FITC-conjugated anti-CD4 monoclonal antibodies (mABs), PE-conjugated anti-HLA-G mABs, PerCPCy5.5-conjugated anti-CD14 mABs, and APC-conjugated anti-CD8 mABs. RESULTS: Critical COVID-19 patients had a significantly lower frequency of CD4+ HLA-G+ T lymphocytes compared with moderate/severe COVID-19 patients (p value < 0.001; SMD, -1.27; 95% CI [-1.86, -0.66]) and healthy controls (p value < 0.05; SMD, -0.69; 95% CI [-1.25, -0.12]). Critical COVID-19 patients had a significantly lower frequency of CD14+ HLA-G+ monocytes compared with moderate/severe COVID-19 patients (p value < 0.001; SMD, -2.09; 95% CI [-2.77, -1.41]) and healthy controls (p value < 0.05; SMD, -0.83; 95% CI [-1.40, -0.25]). However, there was no difference between the groups regarding the frequency of CD8+ HLA-G+ T lymphocytes. CONCLUSION: The increased amount of immunomodulatory HLA-G+ cells may reduce the severity of the disease in moderate/severe COVID-19 patients compared with critical COVID-19 patients.

Innate immunity: Trained immunity and innate allorecognition against the allograft.

The immune system response of transplant recipients is the main cause of allograft rejection; therefore, its suppression seems crucial. Nevertheless, immunosuppressive agents are largely ineffective against innate immune response. Innate immunity is immediately activated after transplantation and contribute to allograft inflammation and rejection. In this regard, understanding the mechanism of activation and targeting the components of innate immunity could improve allograft survival time. In this review, we discuss two scenarios in the innate immunity, i.e., danger and allogeneic signals in the context of both allogeneic and syngeneic graft. Moreover, the mechanisms of innate allorecognition (i.e., signal regulatory protein α-CD47 and paired immunoglobulin-like receptors-MHC I axis) are described, which can improve our clinical decisions to use a better therapeutic strategy.

Increased Levels of serum Pentraxin 3 in Critical Coronavirus Disease-2019 Patients.

Pentraxin 3 (PTX3) and ficolin are the plasma phase of pattern recognition receptors (PRRs) and can activate complement through classical and lectin pathways, respectively, which may contribute to disease severity. This study aimed to investigate the association between PTX3 and ficolin with disease severity in patients with coronavirus disease-2019 (COVID-19). Seventy-three COVID-19 patients and 25 healthy controls were enrolled in this study. The participants were divided into three groups as follows: 14 patients as the intensive care unit (ICU) group, 59 patients as the non-ICU group, and 25 subjects as the healthy control group. The serum levels of PTX3 and ficolin were measured by enzyme-linked immunosorbent assay (ELISA) kits. Patients in ICU and non-ICU groups had significantly higher levels of PTX3 compared to the healthy control group (p = 0.0002 and p = 0.0072, respectively). Patients in the ICU group also had an increased amount of PTX3 (1957 ± 1769 pg/ml) compared to non-ICU patients (1220 ± 1784 pg/ml). However, this difference was not significant. On the other hand, serum levels of ficolin were not different among the three groups. PTX3, as an acute phase protein, may contribute to disease severity. Its probable inflammatory role could result from the high activation of the complement system. On the other hand, it could be suggested that ficolin has no crucial role in the disease severity of COVID-19 patients.

Seroprevalence Estimates of Latent and Acute Toxoplasma Infections in HIV+ People-Call for Action in Underprivileged Communities.

We undertook a comprehensive, systematic review of observational studies to estimate respective seroprevalences of latent and acute Toxoplasma gondii infections in HIV+ people at the global, regional and country levels; related seroprevalence to socio-economic variables and CD4+ cell counts; and assessed temporal changes in prevalence and risk factors for this group. We systematically searched international databases for seroepidemiological surveys between 1 January 1980 and 31 July 2020. We used a random effects model to calculate pooled seroprevalences with 95% confidence intervals (CI), and estimated the numbers of HIV+ people inferred to harbour latent and acute T. gondii infections (LT or AT). We grouped seroprevalence data according to the geographic regions defined by the World Health Organization (WHO) and conducted subgroup and meta-regression analyses of the data. Of a total of 4024 studies identified, 150 and 65 of them met the inclusion criteria for LT and AT in HIV+ people, respectively. The overall, pooled seroprevalences of LT and AT were 37.4% (95% CI, 33.4-41.4) and 1.3% (95% CI, 0.9-1.8%), equating to ~14.2 and 0.5 million HIV+ people, respectively. Most HIV+ people with T. gondii infections originated from Africa, and the highest seroprevalences were in low-income countries with low human development indices. Significant risk factors for toxoplasmosis in HIV+ patients included the consumption of raw/undercooked meat, frequent contact with soil, a low CD4+ T lymphocyte number (<200 cells per µL) and age. Overall, the finding of high seroprevalences of particularly latent T. gondii infection in HIV+ people in underprivileged regions of the world, such as parts of Africa, calls for preventative action. Programs that include routine serological monitoring, counselling, care, animal control and/or prophylactic treatment measures are needed to prevent severe toxoplasmosis from developing in people living with HIV infection. Our study highlights the potential importance of parasite chemoprophylaxis in resource-poor settings, particularly in low-income countries.

TIM-3 as a potential exhaustion marker in CD4+ T cells of COVID-19 patients.

BACKGROUND: COVID-19 causes a range of clinical symptoms from mild to critical and can be life-threatening. Up to now, it has led to many deaths. We aimed to evaluate exhausted markers on CD4+ T cells of COVID-19 patients. METHODS: In this study, we evaluated 44 patients with confirmed COVID-19 disease and 16 healthy individuals. Patients were divided into moderate/severe and critical groups. Peripheral blood mononuclear cells (PBMCs) were isolated and stained by anti-human CD39, PD-1, TIM-3, and anti-human CD4. The percentage of each CD4+  subpopulation was calculated by flow cytometry. Furthermore, we collected clinical information and laboratory data of both control and patient groups. RESULTS: We detected overexpression of TIM-3 on CD4+  T cells in both critical and moderate/severe patients than in healthy individuals (HIs; p < .01 and p < .0001, respectively). CD4+  TIM-3+ CD39+  lymphocytes were significantly higher in the critical patients than in HI (p < .05). Both Patient groups showed lymphopenia in comparison with HI, but CD4+  lymphocytes did not show any significant difference between study subjects. The increased amount of C-reactive protein, erythrocyte sedimentation rate, creatinine, blood urea nitrogen, and neutrophil count was observed in patients compared to HI. CONCLUSION: T cell exhaustion occurs during COVID-19 disease and TIM-3 is the most important exhausted marker on CD4+ T cells.

Posttreatment Downregulation of Type III Interferons in Patients with Acute Brucellosis.

There is a limited number of clinical studies on interferon (IFN) levels in human brucellosis. The novel group of interferons, type III interferons, which consists of four IFN-λ (lambda) molecules called IFN-λ1 or interleukin-29 (IL-29), IFN-λ2 or IL-28A, IFN-λ3 or IL-28B, and IFN-λ4, is not fully known. This study is one of the first studies of IL-28A and IL-29 levels in brucellosis cases at the end of their treatment course. A total of 33 acute brucellosis patients were included in this study. We considered changes in the levels of IL-28A and IL-29 in cases with acute brucellosis before and after treatment with standard therapy that referred to the Ayatollah Rohani Hospital in Babol, northern Iran. Of 33 included patients, 22 (66.6%) were males, and 11 (33.4%) were females. The range of patients' age was 49.21 ± 17.70 years. Serum IL-29 and IL-28A (acute form: 56.4 ± 30.32 pg/mL and 48.73 ± 27.72 pg/mL, respectively, and posttreatment: 40.15 ± 20.30 pg/mL and 38.79 ± 22.66 pg/mL, respectively) levels were elevated significantly in acute brucellosis than after treatment (p < 0.05). These findings indicate that considering biomarker levels in brucellosis patients may indicate the chronicity of infection. In conclusion, we suggest that IL-29 and IL-28A levels may be valuable biomarkers for follow-up patients with brucellosis.

Inhibition of Exosome Release Sensitizes U937 Cells to PEGylated Liposomal Doxorubicin.

Aims: Acute myeloblastic leukemia (AML) is the most common type of acute leukemia in adults. Despite numerous treatment strategies including chemotherapy and radiotherapy, a large number of patients do not respond to treatment and experience relapse. The main problem of these patients is the development of resistance to anti-cancer drugs. Therefore, any endeavor to reduce drug resistance in these patients is of high priority. In general, several mechanisms such as changes in drug metabolic pathways, drug inactivation, drug target alterations and reduced drug accumulation in the cells contribute to drug resistance of cancer cells. In this context, evidence suggests that exosomes could reduce drug resistance by removing drugs from their parent cells. In the present study, we aimed to investigate the effects of exosome release inhibition on the resistance of U937 cells to PEGylated liposomal doxorubicin (PLD). Main Methods: In order to find a suitable ABCG2 (ATP-binding cassette sub-family G member 2) transporter substrate, virtual screening was performed among a list of drugs used in leukemia and PLD was selected. U937 cells were treated with PLD with/without co-treatment with the exosome release inhibitor, GW4869. Released exosomes within different study groups were isolated and characterized to determine the differences between groups. Doxorubicin presence in the isolated exosomes was also measured by high performance liquid chromatography (HPLC) to confirm drug export through the exosomes. Finally, the effect of exosome inhibition on the cytotoxicity of PLD on U937 cells was determined using different cytotoxicity assays including the standard lactate dehydrogenase (LDH) release assay and the flow cytometric analysis of apoptotic and non-apoptotic cell death. Key Findings: GW4869 treatment caused a significant decrease in the exosome release of U937 cells compared to the untreated cells, as evidenced by the reduction of the protein content of the isolated exosomes (P<0.05). Co-treatment with GW4869 significantly increased cytotoxic cell death in the groups treated with 0.5 and 1 µM PLD, compared to the same groups without GW4869 co-treatment (P<0.05). Interestingly, co-treatment with GW4896 and 0.5 µM PLD was enough to induce the same cytotoxic effect as that of the sole 1 µM PLD group. Significance: Our findings showed that U937 cells increase their resistance against the cytotoxic effects of PLD through the exosome-mediated expelling of the drug. Inhibition of exosome release could prevent PLD efflux and consequently increase the vulnerability of the U937 cells to the cytotoxic effects of PLD. Our results along with prior studies indicate that the integration of exosome release inhibitors into the common PLD-containing chemotherapy regimens could significantly lower the required concentrations of the drug and consequently reduce its associated side effects. Further studies are warranted to identify clinically safe inhibitors and investigate their clinical efficacy.

The association between vitamin D and acute rejection in human kidney transplantation: A systematic review and meta-analysis study.

BACKGROUND: Vitamin D (VitD) deficiency is associated with several diseases such as multiple sclerosis, rheumatoid arthritis, respiratory infection, and so forth. In the field of transplantation (kidney transplantation), some studies reported that patients with VitD deficiency are of increased chance of acute rejection, but other studies did not show such a chance. On the other hand, since VitD is a modulatory factor and can reduce the inflammatory response, understanding the exact role of it in transplantation may contribute to tolerance condition in these patients. METHODS: The electronic databases, including PubMed, Scopus, Embase, ProQuest, Web of Science, and Google Scholar, were searched for eligible studies. In general, 14 studies with a total of 4770 patients were included in this meta-analysis. Regarding the methodological heterogeneity, we selected a random-effects combination model. Moreover, OR was chosen as an effect size for this study. RESULTS: After the combination of 14 studies, we showed that patients in the VitD-deficient group had an 82% increased chance of acute rejection compared with patients in the VitD-sufficient group, and this effect was significant (OR 1.82; 95% confidence interval [CI] [1.29, 2.56]; I2 = 52.3%). This result was significant, and, regarding the narrow CI, it can be a conclusive result. Study quality and gender variables were the main sources of inconsistent results in the primary studies. Moreover, using meta-regression, we showed that VitD deficiency (independent from the estimated glomerular filtration rate (eGFR) of patients) increased the chance of acute rejection. CONCLUSION: The normal VitD status of patients a few days before and after transplantation can reduce the chance of acute rejection.

Reduced frequency of T helper 17 and T helper 1 cells and their association with critical coronavirus disease 2019.

There is very little knowledge about the immune responses, particularly cellular immunity to coronavirus disease 2019 (COVID-19). The main objective of this study was to evaluate the frequency of T helper (Th) cell subtypes, including Th1, Th17, and Treg cells, in moderate-to-severe and critical COVID-19 patients compared to healthy controls. Twenty-nine moderate-to-severe and 13 critical patients confirmed for COVID-19, and 15 healthy subjects were included in this study. Interferon-γ (IFN-γ)-producing Th1 and interleukin-17A-producing Th17 and Treg cells in peripheral blood were measured with flow cytometry. The frequency of Th1 and Th17 was significantly decreased in critical patients compared to healthy subjects (aMD: -2.76 and - 2.34) and moderate-to-severe patients (aMD: -1.89 and - 1.89), respectively (p < 0.05). Differences were not significant between moderate-to-severe patients and healthy subjects for both Th1 (p = 0.358) and Th17 (p = 0.535), respectively. In contrast, significant difference was not observed between study subjects regarding the frequency of Treg cells. Patients with critical COVID-19 had a markedly lower Th1/Treg and Th17/Treg ratios compared with the controls and moderate-to-severe cases. Our study showed a dysregulated balance of Th1 and Th17 cells and its relation to the severity of COVID-19.

Linkage of Lambda Interferons in Protection Against Severe COVID-19.

The most recently discovered interferon (IFN) family, type III IFNs or lambda IFNs (IFN-λs) are caused by viral infection and act in mucosal barriers, such as the respiratory tract. In this study, we assessed the serum levels of IFN-λs in new coronavirus disease-2019 (COVID-19) patients. Sixty-four COVID-19 patients were enrolled in this study. All cases were divided into the intensive care unit (ICU) and non-ICU groups according to their symptoms. Fourteen samples of healthy controls were also included. The serum levels of IFN-λ1 and IFN-λ2 were analyzed by specific enzyme-linked immunosorbent assay (ELISA) kits. The concentrations of IFN-λ1 and IFN-λ2 induced in the serum of non-ICU patients (836.7 ± 284.6 and 798.8 ± 301.5 pg/mL, respectively) were higher than found in ICU patients (81.57 ± 34.25 and 48.32 ± 28.13 pg/mL, respectively) (P = 0.004 and P = 0.006, respectively) and healthy controls (85.57 ± 33.63 and 65.82 ± 21.26 pg/mL, respectively) (P = 0.03 and P = 0.04, respectively). Meanwhile, no significant differences were found in the concentration of both cytokines between the ICU patients and healthy controls. We conclude that higher levels of IFN-λs are associated with decreased clinical manifestations in COVID-19 patients. These cytokines could be a promising therapeutic agent to avoid the overwhelming consequences of COVID-19.

Pronounce expression of Tim-3 and CD39 but not PD1 defines CD8 T cells in critical Covid-19 patients.

BACKGROUND: During viral infection, inhibitory receptors play a key role in regulating CD8 T-cell activity. The objective of this research was to investigate programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3), and CD39 exhaustion markers in CD8 T cells of new coronavirus disease-2019 (COVID-19) patients. METHODS: A total of 44 patients with COVID-19 (17 subjects in a critical group and 27 patients in a non-critical group) and 14 healthy controls, who were admitted to Hospitals in Babol, were recruited to the study. In subjects' peripheral blood mononuclear cells (PBMCs), we compared the phenotype of CD8 T lymphocytes, expressing PD-1, TIM-3, or CD39, both alone and in various combinations. RESULTS: The findings showed that the percentage of CD8+ cells was significantly lower in patients. Critical and non-critical patients were more likely than healthy controls to have an escalated frequency of CD8+ TIM-3+, CD8+ CD39+, and CD8+ TIM-3+ CD39+ cells. No significant differences were observed between all groups in the CD8+ PD-1+ cell counts. There was also no difference between three groups regarding the counts of CD8+ TIM-3+ PD-1+, CD8+ PD-1+ CD39+, and CD8+ TIM-3+ PD-1+ CD39+ cells. The counts of non-exhausted cells were significantly lower in critical and non-critical individuals compared to the healthy individuals' value. CONCLUSION: Patients, infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), altered exhausted CD8 T lymphocytes with CD39 and TIM-3 exhaustion markers, which may account the dysregulated immune response found in COVID-19.

Decreased Frequency of CD8+HLA-G+ T Cell in the Peripheral Blood of Primary Unexplained Infertile Females.

Most of the findings have focused on the importance of CD4+HLA-G+ and CD8+HLA-G+ regulatory T cells (Treg) during pregnancy. It has been demonstrated that these HLA-G+ T cell subsets could induce maternal immune tolerance against semi-allogenic conceptus during pregnancy. There are only a few experiments regarding the Treg cells in the context of unexplained infertility (UI). Thirty-five participants including 18 primary unexplained infertile and 17 fertile females were enrolled in this study. A total of 3-5 ml blood samples were taken, and peripheral blood mononuclear cells (PBMCs) were separated by using Ficoll. Using a flow cytometer, the frequency of CD4+HLA-G+ and CD8+ HLA-G+ T cells was assessed in the peripheral blood samples of primary unexplained infertile and fertile females. Our results showed that the frequency of CD8+HLA-G+ Treg cells was significantly lower in primary unexplained infertile females than fertile females (P = 0.048). Although the frequency of CD4+HLA-G+ Treg cells in the primary unexplained infertile females was lower than fertile females, the difference was not statistically significant (P = 0.25). Regarding the important role of CD8+HLA-G+ Treg cells during pregnancy and its decrease in females with primary UI, it seems that reduced CD8+ HLA-G+ Treg cells could be a leading immunological factor in the context of infertility. Nevertheless, more researches are needed in this field.

Under-expression of microRNA-146a and 21 and their association with Crohn's disease.

MicroRNAs (miRNAs) can post-transcriptionally regulate gene expression and are involved in the immune response. Excessive immune response to the gut microbiota plays a major role in the pathogenesis of Crohn's disease (CD). Regarding the role of miRNAs in immune response, this study aimed to investigate the contribution of miRNAs in the pathogenesis of CD. A total of 53 participants, including 23 CD patients and 30 healthy controls (HCs) were enrolled in this study. miRNAs, including miR-21, miR-29a, miR-29b, miR-31, miR-146a, miR-155, miR-181a, and miR-181c were evaluated via TaqMan MicroRNA Assays. Among the eight miRNAs, the amounts of miR-146a and miR-21 were significantly decreased in the CD patients relative to HC subjects. Moreover, we showed that there was a negative correlation between miR-146a and Harvey-Bradshaw index (HBI), as well as a positive correlation of miR-21 and miR-29b with HBI. Under-expression of miR-146a and miR-21, which are critical for the regulatory function of regulatory T cells (Tregs), is remarkably associated with CD.