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The footprint of cytokines is evident in almost every biological process, such as development, as well as the pathogenesis of the different diseases, immune responses to pathogens, etc. These small proteins are categorized into different functional classes; for instance, they can play a pro-inflammatory or anti-inflammatory role in different situations, or they can confer a polarization to the immune system. Interleukin (IL)-27 is a member of the IL-12 family. Antigen-presenting cells are the primary source of IL-27 production, which exerts its effects by bindings to the IL-27 receptor expressed on the surface of target cells. Interaction of IL-27 and IL-27 receptor leads to activation of the JAK-STAT and p38 MAPK signaling pathways. Most studies focused on the inflammatory effects of this cytokine, but gradually anti-inflammatory effects were also revealed for this cytokine, which changed the traditional perception of the function of this cytokine. The functionality of IL-27 in the pathogenesis of rheumatic diseases has been attributed to a double-blade sword. Hence, novel therapeutic approaches have been devised targeting IL-12 family that has been accompanied with promising results. In this review, we focused on the inflammatory and anti-inflammatory properties of IL-27 in different autoimmune rheumatologic diseases and its plausible therapeutic potentials. Show less

To investigate serum levels of interleukin (IL)-12 (Th1 cytokine), IL-27 (an immunomodulatory cytokine), IL-4 (suppressor of Th1-cell growth), IL-13 (a stimulatory signal for Th2 cytokines), and IL-33 (an epithelial cell-derived cytokine) and their relations with the disease activity in Behcet's Disease (BD). Four groups, each composed of 20 participants were enrolled in the study; active ocular BD (Group-A), ocular BD in remission (Group-B), nonocular BD in remission (Group-C) and healthy controls (Group-D). IL levels were compared between the study groups and their correlation with the disease activity parameters were analyzed. IL-13 and IL-33 were higher in Group-A. IL-27 was lower in all BD groups. Additionally, IL-13 and IL-33 levels were positively correlated with disease activity parameters. These findings show Th2 dominance in the active phase of BD. Besides, decreased levels of IL-27, and presumably, its protective anti-inflammatory effect in all study groups may exert a new pathologic finding in BD. Show less

Inflammation is recognized as representing a double-edged sword in terms of tumor growth, in some instances contributing to attenuation of growth and in others to enhanced progression and metastasis. Extracellular signals, released by cells within the tumor microenvironment (TME), including cancer cells themselves, as well as infiltrating immune cells, stromal cells, and other components of the extracellular matrix, all can contribute to reshaping the tumor microenvironment (TME) and tumor growth/survival. Most recently, attention has centered on contributions in the TME made by the pro-inflammatory interleukin 17 (IL-17) and the T cells (Th17) and non-T cells which produce this cytokine, as well as the target cells (IL-17 receptor positive, IL-17R Show less

We have examined the role of a novel targeted cytokine, interleukin-27 (IL-27), modified at the C terminus with a dual targeting and therapeutic heptapeptide, in treating prostate cancer. IL-27 has shown promise in halting tumor growth and mediating tumor regression in several cancer models, including prostate cancer. We describe our findings on the effects of targeted IL-27 gene delivery on prostate cancer cells Show less

The interleukin-12 (IL-12) family consists of four members, namely, IL-12, IL-23, IL-27, and IL-35. The aim of this study was to examine the expression of circulating IL-12, IL-23, IL-27, and IL-35 in hypertensive patients. Blood samples were collected from hypertensive patients and nonhypertensive (control) subjects, and protein multifactorial monitor kits were used to measure the plasma IL-12, IL-23, IL-27, and IL-35 levels in each sample. In addition, all enrolled subjects underwent ambulatory blood pressure monitoring (ABPM) and vascular stiffness. Hypertensive patients exhibited higher IL-12, IL-23, and IL-27 levels and lower IL-35 levels than control subjects; IL-12, IL-23, and IL-27 levels were positively correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP), while IL-35 levels were negatively correlated with SBP and DBP. IL-12, IL-23, and IL-27 levels gradually increased in patients with grade I, II, and III hypertension, while IL-35 levels gradually reduced. According to the ABPM results, hypertensive patients were divided into the dipper and nondipper hypertension groups; IL-12, IL-23, IL-27, and IL-35 levels showed no differences between the two groups, but IL-12, IL-23, and IL-27 levels in both groups increased compared with those in the control group, while IL-35 levels decreased. Additionally, the expression of these IL-12 family members was influenced by many clinical factors and was independently associated with the occurrence of carotid atherosclerotic plaques. The changes in IL-12, IL-23, IL-27, and IL-35 levels were not associated with the presence of the nondipper type but were closely associated with the development of carotid atherosclerotic plaque in hypertensive patients. Show less

Host immune response have a pivotal role in the course of Mycobacterium tuberculosis (Mtb) infection. IL27 plays both pro-inflammatory and anti-inflammatory activities in infectious diseases via STAT1/STAT3 mechanism. To investigate the association of single nucleotide polymorphisms (SNPs) of IL27 and STAT3 on the susceptibility of tuberculosis, we conducted a large size of case-control study in western Chinese Han population. A total of seven SNPs were genotyped using multiplex ligation detection reaction method in 900 patients with tuberculosis and 1534 healthy controls. Variants of three SNPs (rs181206, rs17855750, rs26528) within IL27 gene, the genotype and allele frequencies of rs17855750 were significantly different (p = .013, p = .004, respectively) between the TB patients and healthy controls. Subjects carrying C allele for rs17855750 showed a decreased tuberculosis risk (OR = 0.75, 95% CI = 0.62-0.91, p = .004). Genetic model analysis revealed that dominant modal was associated with lower TB risk (OR = 0.74, 95% CI = 0.60-0.92, p = .042). Haplotype of ACG (representing rs181206, rs17855750 and rs26528) showed a reduced risk to TB (OR = 0.79, 95% CI = 0.65-0.96, p = .017). There were no significant differences between TB cases and healthy controls in the variants of four SNPs (rs1053005, rs2293152, rs744166, rs4796793) within STAT3 gene. The polymorphisms of IL27, rs17855750, but not rs181206 and rs26528, plays a protective role on the susceptibility to TB. Show less

Ectopic lymphoid structures (ELS) develop at sites of infection, autoimmunity, and cancer. In patients with Sjögren's syndrome (SS), ELS support autoreactive B cell activation and lymphomagenesis. Interleukin-27 (IL-27) is a key regulator of adaptive immunity and limits Th17 cell-driven pathology. We undertook this study to elucidate the role of IL-27 in ELS formation and function in autoimmunity using a murine model of sialadenitis and in patients with SS. ELS formation was induced in wild-type and Il27ra In experimental sialadenitis, Il27ra Our data indicate that the physiologic ability of IL-27 to limit the magnitude and function of ELS through control of Th17 cell expansion is severely impaired in SS patients, highlighting a defective immunoregulatory checkpoint in this condition. Show less

A lot of research nowadays is dedicated to the problem of habitual pregnancy loss, and this attention is dictated by the continued high frequency of this condition. The pathogenesis of habitual pregnancy loss is very complicated and includes many factors, at present especially close attention is paid to immune aspects. It is considered, that cytokine imbalance might play a key role in the pathogenesis of habitual pregnancy loss. Examination of 38 pregnant women was carried out at 5-12 weeks of gestation. The main group consisted of 17 women with habitual miscarriage and the threat of interruption at the time of the examination, the control group consisted of 21 women with uncomplicated pregnancy and a favorable obstetric history. As the material for investigation peripheral blood was used. Serum level of a complex of cytokines IL-β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-17A, IL-18, IL-21, IL-22, IL-23, IL-27, IFNγ, TNFα, GM-CSF was assessed on the Luminex 200 multiplex fluorescence analyzer (Luminex Corporation, USA). The significant differences in the serum level of IL-1β, IL-22, IL-23 и IL-27 were observed between the groups, in the main group their level was higher comparing to that of healthy pregnant women. When evaluating the cytokines serum level, fairly high values of IL-27 (in 25%of cases) (p<0,05), TNFα - (in 18% of cases) (p>0,05) were found in the main group, while in the control group they were not registered. Significant differences in the serum level of IL-2, IL-4, IL-9, IL-12p70, IL-18 and IFNγ were not noted in the compared groups (p>0,05). The simultaneous increase in the serum level of pro- and anti-inflammatory cytokines observed in our study can be explained by both an increase in the immune response and triggering of fetoprotection mechanisms. Inadequate cytokine regulation may be a prerequisite for the development of conditions for the development of a threat of termination of a real pregnancy in women with habitual miscarriage. Show less

Mycobacterial diseases of cattle are responsible for considerable production losses worldwide. In addition to their importance in animals, these infections offer a nuanced approach to understanding persistent mycobacterial infection in native host species. Show less

Intestinal microbes and their metabolites affect the development of colorectal cancer (CRC). Short-chain fatty acids are metabolites generated by intestinal microbes from dietary fiber. We investigated the mechanisms by which free fatty acid receptor 2 (FFAR2), a receptor for short-chain fatty acids that can affect the composition of the intestinal microbiome, contributes to the pathogenesis of CRC. We performed studies with Apc Apc Loss of FFAR2 promotes colon tumorigenesis in mice by reducing gut barrier integrity, increasing tumor bacterial load, promoting exhaustion of CD8 Show less

Cytokines have regulatory crosstalk with CMV infection leading to manage of post-liver transplantation virus-related outcomes. To investigate the link between IL-21, IL-23 and IL-27 mRNA and protein level with active CMV infection, which was evaluated in reactivated and non-reactivated liver transplant recipients. Two groups of liver transplant recipients were enrolled in this study-54 without and 15 with active CMV infection. 3 EDTA-treated blood samples were taken on day 1, 4, and 7 post-liver transplantation. Plasma and buffy coats of all samples were separated. All samples were analyzed for CMV reactivation using antigenemia technique. The separated plasma of positive samples was used for viral DNA extraction and protein evaluation. For evaluating the mRNA expression level by real-time PCR, RNA extraction and cDNA synthesis were done for all samples. Also, the protein level of studied genes was estimated by ELISA. The expression level of IL-21, IL-23A and IL-27A cytokine genes was increased in CMV reactivated liver transplant recipients in comparison with CMV non-reactivated ones; IL-27A expression pattern was significant (p=0.001) at all sampling times. IL-21 significantly increased on the 2 Elevation in the expression level of IL-21, IL-23A and IL-27A mRNA and protein level in CMV reactivated patients emphasized on the antiviral role of these cytokines in CMV reactivated liver transplant recipients. Show less

Bacteria-host interactions are mediated by different microbial associated molecular patterns which are most often surface structures such as, among others, exopolysaccharides (EPSs). In this work, the capability of two isogenic EPS-producing Show less

Interleukin-27 (IL-27), which belongs to IL-12 family, influences the function of T cells (Tregs) through regulating the expression, and function of forkhead box P3 (FoxP3). In this study, we detected the IL-27 serum levels in 59 myasthenia gravis (MG) patients and 35 healthy controls (HCs). Among them, 32 MG patients received immunoglobulin intravenous (IVIG) injections (0.4 g/kg per day for 5 consecutive days). IL-27 levels were collected before and after the treatments and subjected to a comparative study. Finally, we assessed the correlations of IL-27 levels with the clinical characteristics of MG. As a result, serum IL-27 levels were significantly higher in MG patients than those in the HCs. Meanwhile, significant reduction was detected after the IVIG treatment. IL-27 levels positively correlated with both MG activities of daily living and quantitative MG score. IL-27 may participate in the pathogenesis of MG and can be used as an early marker for the diagnosis and prognosis of MG. In addition, IL-27 can be used as a target for MG treatment through the regulation of specific immune signaling and maintaining immune homeostasis. Show less

Mechanisms underlying the role of non-human leukocyte antigen (HLA) genetic risk variants in type 1 diabetes (T1D) are poorly understood. We aimed to test the association between methylation and non-HLA genetic risk. We conducted a methylation quantitative trait loci (mQTL) analysis in a nested case-control study from the Dietary Autoimmunity Study in the Young. Controls (n = 83) were frequency-matched to T1D cases (n = 83) based on age, race/ethnicity, and sample availability. We evaluated 13 non-HLA genetic markers known be associated with T1D. Genome-wide methylation profiling was performed on peripheral blood samples collected prior to T1D using the Illumina 450 K (discovery set) and infinium methylation EPIC beadchip (EPIC validation) platforms. Linear regression models, adjusting for age and sex, were used to test to each single nucleotide polymorphism (SNP) -probe combination. Logistic regression models were used to test the association between T1D and methylation levels among probes with a significant mQTL. A meta-analysis was used to combine odds ratios from the two platforms. We identified 10 SNP-methylation probe pairs (false discovery rate (FDR) adjusted P < .05 and validation P < .05). Probes were associated with the GSDMB, C1QTNF6, IL27, and INS genes. The cg03366382 (OR: 1.9, meta-P = .0495), cg21574853 (OR: 2.5, meta-P = .0232), and cg25336198 (odds ratio: 6.6, meta-P = .0081) probes were significantly associated with T1D. The three probes were located upstream from the INS transcription start site. We confirmed an association between DNA methylation and rs689 that has been identified in related studies. Measurements in our study preceded the onset of T1D suggesting methylation may have a role in the relationship between INS variation and T1D development. Show less

IL-27 is an anti-inflammatory cytokine that has been shown to have potent anti-tumor activity. We recently reported that systemic delivery of IL-27 using recombinant adeno-associated virus (rAAV) induced depletion of Tregs and significantly enhanced the efficacy of cancer immunotherapy in a variety of mouse tumor models. A potential caveat of systemic delivery of IL-27 using rAAV is that there is no practical method to terminate IL-27 production when its biological activity is no longer needed. Therefore, in this work, we tested if directly injecting AAV-IL-27 into tumors could lead to similar anti-tumor effect yet avoiding uncontrolled IL-27 production. We found that high levels of IL-27 was produced in tumors and released to peripheral blood after AAV-IL-27 intra-tumoral injection. AAV-IL-27 local therapy showed potent anti-tumor activity in mice bearing plasmacytoma J558 tumors and modest anti-tumor activity in mice bearing B16.F10 tumors. Intra-tumoral injection of AAV-IL-27 induced infiltration of immune effectors including CD8 Show less

To determine the possible associations of polymorphisms in interleukin (IL)-8 (rs4073 T/A), IL-10 (rs1800896 A/G), IL-22 (rs1179251 C/G and rs2227485 C/T), IL-27 (rs17855750 T/G), and transforming growth factor beta 1 (TGFß1) (rs1800469 C/T) with colorectal cancer (CRC) susceptibility in Saudi patients. The case-control study was carried out between July 2019 and January 2020 in King Khaled University Hospital, Riyadh, Saudi Arabia. A total of 70 patients with CRC and 70 healthy controls were included  in  the  study.  Single nucleotide polymorphisms of promoter regions were determined using TaqMan genotyping assays. A statistically significant reduction in CRC risk was identified for carriers of the IL-10 (rs1800896 A/G) AG genotype, IL-22 (rs1179251 C/G) G allele, IL-27 (rs17855750 T/G) G allele and TGFß1 (rs1800469 C/T) CT and TT genotype. While IL-10 (rs1800896 A/G) AA genotype and TGFß1 (rs1800469 C/T) CC genotype were significantly associated with increased susceptibility to CRC. No significant associations were identified between the cytokine polymorphisms of IL-8 (rs4073 T/A) and IL-22 (rs2227485 C/T), and CRC risk. Conclusion: Our findings indicate a significant impact of IL-10 (rs1800896 A/G), IL-22 (rs1179251 C/G), IL-27 (rs17855750 T/G) and TGF-ß1 (rs1800469 C/T) polymorphisms on risk of CRC; while the IL-8 (rs4073 T/A) and IL-22 (rs2227485 C/T) and polymorphisms were not associated with CRC risk. Show less

Cytokines are one of the first immunotherapeutics utilized in trials of human cancers with significant success. However, due to their significant toxicity and often lack of efficacy, cytokines have given their spotlight to other cancer immunotherapeutics such as immune checkpoint inhibitors. Nevertheless, only a subset of cancer patients respond to checkpoint inhibitors. Therefore, developing a novel cytokine-based immunotherapy is still necessary. Among an array of cytokine candidates, IL-27 is a unique one that exhibits clear anti-tumor activity with low toxicity. Systemically delivered IL-27 by adeno-associated virus (AAV-IL-27) is very well tolerized by mice and exhibits potent anti-tumor activity in a variety of tumor models. AAV-IL-27 exerts its anti-tumor activity through directly stimulation of immune effector cells and systemic depletion of Tregs, and is particularly suitable for delivery in combination with checkpoint inhibitors or vaccines. Additionally, AAV-IL-27 can also be delivered locally to tumors to exert its unique actions. In this review, we summarize the evidence that support these points and propose AAV-delivered IL-27 as a potential immunotherapeutic for cancer. Show less

To investigate the effect of IL-27 on Th17 cells in patients with henoch-schönlein purpura（HSP） in order to further elucidate the pathogenesis. Fifty patients with HSP treated in our hospital from April 2019 to July 2019 were selected as HSP group, and 30 volunteers underwent physical examination at the same time were selected as control group. The proportion of Th17 cells in peripheral blood of HSP group and healthy control group was determined by flow cytometry (FCM). A total of 27 HSP patients were selected, and candidate peripheral blood mononuclear lymphocytes (PBMC) were co-cultured with exogenous rhIL-27, and the ratio of Th17 cells was detected by flow cytometry. The proportion of Th17 cells in the peripheral blood of HSP patients with acute phase was (1.57±0.54)%, which was significantly higher than that of the control group (0.86±0.40)% (t=-6.298, P<0.001), and the proportion of Th17 cells was decreased significantly after rhIL-27 co-culture (1.39%±0.52% vs 0.98%±0.44%)(P<0.05). IL-27 can reduce the level of Th17 cells in patients with HSP, which may be involved in the pathogenic process of HSP and play a protective role in the development of the disease. Show less

Asthma-COPD overlap (ACO; previously referred to as asthma-COPD overlap syndrome) is characterized by persistent airflow limitation consistent with COPD, together with several distinguishing features of asthma. Asthma-COPD overlap syndrome is a condition of mixing symptoms of asthma and COPD, because of its complexity, it is difficult to find effective diagnostic markers in clinic. Our aims were to detect the expression of serum cytokines in patients with asthma, explore the diagnostic potential of differential serum cytokines in ACOS. Ninety asthmatic patients were divided into ACOS group and non-ACOS group according to the major and minor criteria of ACOS, 15 kinds of cytokines including IL-3, IL-4, IL-8, IL-9, IL-13, IL-17A, VEGFA, VEGFC, VEGFD, bFGF, Fit-1 PIGF, Tie-2 were detected by MSD, and IL-27 and TGF-beta were determined by ELISA assay. The serum levels of IL-9, VEGFA and PIGF in patients with ACOS were significantly higher than those in non-ACOS group ( The results suggested that IL-8 was highly sensitive and VEGFA was highly specificity, both of which could be used as biomarkers for the diagnosis of ACOS. Show less

The authors informed the journal that an error occurred in their manuscript.Figure 3C was mistakenly merged by the authors.The new version of the Figure 3C is as below.Reference:1. Meng Zhang, Xiuxiu Tan, Junjie Huang, Zekai Ke, Yukun Ge, Hu Xiong, Wei Lu, Lu Fang, Zhiming Cai, Song Wu: Association of 3 Common Polymorphisms of IL-27 Gene with Susceptibility to Cancer in Chinese: Evidence From an Updated Meta-Analysis of 27 Studies. Med Sci Monit 2015; 21: 2505-2513. DOI: 10.12659/MSM.895032. Show less

In our previous study, a Seesaw model was proposed for the fluctuation of crucial anti- (IL-10) and pro-inflammatory (Il-6 & IL-17A) cytokines through vitamin D3. In this paper, however, it is intended to extend the mentioned model by assessing the expression mRNA levels of IL-27 and TGF-β1 as well as the changes of plasma levels of IL-27, TGF-β1, IL-17A, IL-10, and IL-6 after treatment by vitamin D3. Venous blood samples were drawn from Healthy Participants (HP, n = 25) and First-Degree Relative Participants (FDRP, n = 25) as control groups and Multiple Sclerosis Participants (MSP, n = 25) before and after eight weeks of supplementation with 50000 IU vitamin D3. The mRNA expression and plasma concentrations were gauged by using Real-Time PCR and ELISA assay, respectively. The mRNA surfaces of IL-27, as well as TGF-β1, were up-regulated. However, the plasma levels of TGF-β1, IL-17A, and IL-6 were significantly different among the three groups. In addition, the plasma levels of IL-27, TGF-β1, IL-10, IL-17A, and IL-6 significantly changed following the administration of vitamin D3. The findings of this paper illustrate that anti-inflammatory cytokines could have a key role in immunomodulatory functions due to their anti-inflammatory functions. To conclude, this might contribute to preventing the pathophysiological process of MS. Also, the proposed model could be used as a preventive way on disposed people to multiple sclerosis, particularly in first degree relatives of these patients. Show less

IL-27, a heterodimeric cytokine composed of the p28 subunit and Epstein-Barr virus-induced gene 3 (EBI3), acts as a potent immunosuppressant and thus limits pathogenic inflammatory responses. IL-27 is upregulated upon Show less

Members of the IL-6/IL-12 cytokine family are critical regulators of innate and adaptive immunity and have emerged as key players controlling inflammatory and autoimmune disorders. This cytokine family comprises of IL-12, IL-23, IL-27, and IL-35, each consisting of distinct α- and β-cytokine subunits that form heterodimers. A new member of this family, IL-39, was identified in the murine species and was shown to consist of the IL-23p19 and Epstein-Barr Virus-induced 3 (EBI3) subunits. Subsequently, it was shown that IL-39 was implicated in the immunopathogenesis of murine experimental lupus erythematosus. The existence of IL-39 in the human system has yet to be confirmed. Based on the clinical success of IL-23p19 neutralizing approaches in moderate-to-severe psoriasis, anti-IL-23p19 antibodies in the clinic may not only neutralize IL-23, but additionally IL-39, implying that IL-39 might also contribute to the pathogenesis of psoriasis. It is therefore pivotal to demonstrate IL-39 expression and to characterize its function in the human system. In this study, we provided evidence for the existence of secreted heterodimeric p19 and EBI3 complexes in supernatants originating from p19 and EBI3 transfected HEK293FT cells. We attempted to detect IL-39 expression from stimulated human primary B cells, human keratinocytes and in vitro polarized human macrophages. Whereas, the expression of p19 and EBI3 mRNA was elevated, we failed to detect p19 and EBI3 heterodimers. Functional assays were conducted with conditioned media containing human IL-39 or with a human recombinant IL-39 Fc protein. Immune cells targeted by IL-39 in mouse, such as neutrophils and PBMCs, did not respond to human IL-39 stimulation and IL-39 failed to activate STAT3 in a reporter cell line. These results suggest that, while the secretion of p19/EBI3 complexes can be forced in human cells, it is secreted below the lower quantity of detection or it has no functional role. Show less

This study investigates the potential of a hydrolysate of ovalbumin with pepsin (OP) to preclude Th2-type immunity by the enhancement of tolerogenic dendritic cells (DCs) and regulatory T (Treg) cells. Through Toll-like receptor (TLR) stimulation, OP enhances the retinoic acid pathway on DCs by means of the induction of aldehyde dehydrogenase enzymes and transforming growth factor beta (TGF-β), and it confers upon DC the ability to upregulate interleukin 10 (IL-10) as well as other tolerance-promoting mediators downstream of TRL signalling, such as IL-27, IL-33, Notch ligands, OX40L, and the transcription factors IRF4 and IRF8. OP-conditioned DCs induce the expansion of Foxp3+ and Tr1 cells in co-culture with CD4+ T cells. Furthermore, OP directly conditions CD4+ T cells from naïve mice, without the mediation of DCs, to express aldehyde dehydrogenase (ALDH) enzymes and, in the presence of the Th2 cytokine IL-4 and exogenous TGF-β, it enhances Foxp3 expression. It is noteworthy that, on CD4+ T cells isolated from egg-allergic mice, OP significantly enriches the levels of Foxp3+ and Foxp3+ RORγt+ CD4+ T cells. In conclusion, we show that food peptides may work, analogously to microbial-driven signals, through TLRs, to promote a tolerogenic phenotype on cells of the innate and adaptive immune system, a property that is further enhanced in the context of a Th2 cytokine-rich environment. Show less

The lacuna in the knowledge of immunobiology, especially in visceral infections that are fatal if left untreated, are a major hurdle in getting a vaccine candidate for leishmaniasis. Till date, only a few drugs are available to combat human leishmaniasis and a vaccine candidate either prophylactic or preventive is still awaited. Therefore, identification of host and parasitic factors involved in the regulation of specific immune mechanisms are essentially needed. In this study, we observed that CD200-CD200R immune inhibitory axis regulates host macrophages effectors properties and helps antigen experienced T cells (CD4 Show less

Myeloid-derived growth factor (MYDGF), which is produced by bone marrow-derived cells, mediates cardiac repair following myocardial infarction by inhibiting cardiac myocyte apoptosis to subsequently reduce the infarct size. However, the function of MYDGF in the incretin system of diabetes is still unknown. Here, loss-of-function and gain-of-function experiments in mice revealed that MYDGF maintains glucose homeostasis by inducing glucagon-like peptide-1 (GLP-1) production and secretion and that it improves glucose tolerance and lipid metabolism. Treatment with recombinant MYDGF increased the secretion and production of GLP-1 in STC-1 cells in vitro. Mechanistically, the positive effects of MYDGF are potentially attributable to the activation of protein kinase A/glycogen synthase kinase 3β/β-catenin (PKA/GSK-3β/β-catenin) and mitogen-activated protein kinase (MAPK) kinases/extracellular regulated protein kinase (MEK/ERK) pathways. Based on these findings, MYDGF promotes the secretion and production of GLP-1 in intestinal L-cells and potentially represents a potential therapeutic medication target for type 2 diabetes. Show less

Interleukin-27 (IL-27) is an immunoregulatory cytokine that suppresses inflammation through multiple mechanisms, including induction of IL-10, but the transcriptional network mediating its diverse functions remains unclear. Combining temporal RNA profiling with computational algorithms, we predict 79 transcription factors induced by IL-27 in T cells. We validate 11 known and discover 5 positive (Cebpb, Fosl2, Tbx21, Hlx, and Atf3) and 2 negative (Irf9 and Irf8) Il10 regulators, generating an experimentally refined regulatory network for Il10. We report two central regulators, Prdm1 and Maf, that cooperatively drive the expression of signature genes induced by IL-27 in type 1 regulatory T cells, mediate IL-10 expression in all T helper cells, and determine the regulatory phenotype of colonic Foxp3 Show less