Expression of IL-35 and its regulatory effects on Th9 cells in patients with type 1 diabetes mellitus / 中华微生物学和免疫学杂志

Objective:To investigate the changes in IL-35 expression in patients with type 1 diabetes mellitus (T1DM) and to analyze the role of IL-35 in regulating Th9 cells.Methods:Thirty-one T1DM patients and 13 controls were enrolled. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated. The levels of IL-35 and IL-9 in plasma were measured by ELISA. The expression of IL-35 subunits, EBI3 and IL-12p35, as well as Th9 transcription factor PU.1 at mRNA level was detected by real-time PCR. The percentages of Th9 cells were measured by flow cytometry. Changes in cell proliferation, the percentage of Th9 cells, PU.1 expression at mRNA level and IL-9 secretion were detected after stimulating PBMCs from T1DM patients and controls with recombinant human IL-35. CD4 + CCR4 -CCR6 -CXCR3 - cells and CD8 + T cells were isolated from PBMCs of 11 T1DM patients. CD4 + CCR4 -CCR6 -CXCR3 - cells were first stimulated with recombinant human IL-35 and then co-cultured with CD8 + T cells. IFN-γ and TNF-α in the culture supernatants were measured by ELISA. Perforin and granzyme B secretion was measured by enzyme-linked immunospot assay. Student′s t-test, paired t-test or LSD- t test was used for statistical analysis. Results:Plasma IL-35 level was lower in T1DM patients than in controls [(67.13±9.94) pg/ml vs (97.77±23.61) pg/ml, P<0.000 1]. Compared with controls, T1DM patients had decreased expression of EBI3 and IL-12p35 at mRNA level in PBMCs ( P<0.000 1). The percentage of Th9 cells, PU.1 expression at mRNA level and plasma IL-9 level were increased in T1DM patients as compared with those in controls [(3.47±0.99)% vs (2.76±0.75)%, P=0.029; P<0.000 1; (99.08±11.85) pg/ml vs (86.38±12.72) pg/ml, P=0.002 8]. IL-35 had no significant influence on the proliferation of PBMCs from both T1DM patients and controls ( P>0.05). The percentage of Th9 cells and PU.1 expression at mRNA level in PBMCs from T1DM patients were down-regulated in response to IL-35 stimulation ( P<0.01), while no significant difference was observed in the control group ( P>0.05). IL-9 secretion by PBMCs was down-regulated in response to IL-35 stimulation in both T1DM and control groups ( P<0.01). CD4 + CCR4 -CCR6 -CXCR3 - cells promoted the secretion of IFN-γ, TNF-α, perforin and granzyme B by CD8 + T cells from T1DM patients ( P<0.05), but the effects could be inhibited by IL-35 ( P<0.05). Conclusions:Decreased IL-35 in T1DM patients could not exert effective immunosuppressive activity, leading to the enhancement of Th9 cell activity and inflammatory injury.

Anti-Allergic Rhinitis Mechanism of Bikangfu via Regulation of IL-35/STAT3， Inhibition of Eosinophil Activation and Improvement of Immune Function / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of interleukin-35（IL-35）/signal transducer and activator of transcription 3（STAT3）inhibition of eosinophil activation against allergic rhinitis（AR） by Bifukang. MethodOne hundred patients were randomly divided into a control group and a treatment group，50 cases in each group. The control group was given mometasone furoate nasal spray，and the treatment group was given Bifukang by nasal packing. The course of treatment was 28 days. The clinical efficacy，nasal classification and visual analogue scale（VAS） score of the two groups were observed before and after treatment. Enzyme linked immunosorbent assay（ELISA） was used to detect the expression levels of inflammatory factors ［interleukin（IL）-4，IL-10，IL-17，IL-35］ and Eotaxin and CC chemokine receptor-3（CCR3）in serum and nasal secretion of the two groups. The expression levels of STAT1，STAT3 and STAT4 were detected by real-time polymerase chain reaction（Real-time PCR）.The content of immunoglobulin G（IgG） and the ratio of CD4+/CD8+were detected by ELISA and flow cytometry. ResultAfter treatment， compared with before treatment， the levels of IL-4 and IL-17 in serum and nasal secretion in 2 groups were decreased， while the levels of IL-10 and IL-35 were increased （P<0.05， P<0.01）. The expression of STAT1， STAT2 and STAT3 in nasal secretions were significantly decreased （P<0.05）. IgG and CD4+/CD8+ were decreased， and the differences were statistically significant （P<0.05， P<0.01）.After treatment，compared with the control group，the levels of IL-4 and IL-17 in serum and nasal secretions of the treatment group were decreased，while the levels of IL-10 and IL-35 were increased （P<0.05）. The expression of STAT1，STAT3 and STAT4 in the treatment group was significantly inhibited compared with the control group after treatment （P<0.05）. In addition， the post-treatment serum CD4+/CD8+ and immunoglobulin G （IgG） levels were reduced in the treatment group compared with those of the control group （P<0.05， P<0.01）. During the treatment，there were no abnormal changes in heart，liver，kidney function and routine blood and urine tests in the two groups. ConclusionBifukang has a good effect on allergic rhinitis，and its mechanism may be related to the regulation of IL-35/STAT3 pathway，the inhibition of eosinophil activation and the improvement of related immune function.

Decreased serum levels of IL-27and IL-35 in patients with Graves disease

ABSTRACT Objectives Graves' disease (GD) is an autoimmune disease causing the overproduction of the thyroid hormone from thyroid gland. This disease is mainly the result of the production of antibodies against TSH receptors. Cytokines play an important role in orchestrating the pathophysiology in autoimmune thyroid disease. The regulatory role of IL-12 on TH1 cells has been proven. IL-27 and IL-35, members of IL-12 cytokine family, are two cytokines that have been newly discovered. IL-35 has been identified as a novel immunosuppressive and anti-inflammatory cytokine while IL-27 has both inflammatory and anti-inflammatory functions. The objective of the current study was to examine the changes in the serum level of the foregoing cytokines in GD patients in comparison to healthy controls. Materials and methods In this study, serum levels of IL-27 and IL-35 were determined by an ELISA method; anti TPO and anti Tg were measured by an RIA method in 40 new cases of Graves's disease. The findings were compared with 40 healthy controls. Results The results showed a significant difference between IL-27 and IL-35 regarding their serum levels with P values of 0.0001 and 0.024, respectively; anti TPO and anti Tg levels of the cases were also significantly different from controls (p < 0.001). Conclusion The reduction in the serum levels of IL-27 and IL-35 in GD patients compared to normal subjects suggests the possible anti-inflammatory role of these cytokines in GD.

Expression and significance of IL-35 in chronic sinusitis with nasal polyps / 中国免疫学杂志

Objective:To observe the expression of IL-35 in chronic sinusitis with nasal polyps(CRSwNP),and to complement the pathogenesis.Methods:The clinical data and nasal polyp tissues of CRSwNP who were hospitalized from May 2016 to April 2017 were randomly selected.The subjective symptoms were scored by visual analogue scale (VAS),the nasal endoscopy score by Lanza-Kennedy,and the CT score by Lund-Mackay.The IL-35 mRNA were detected by Real-time PCR in nasal polyp tissues,while the IL-35, IL-17 and IL-10 were detected by ELISA.Results: A total of 51 patients of the clinical data and nasal polyp tissues were collected.Among them,30 males and 21 females had the mean age of (43.3 ± 15.1) years,the VAS score was (5.5 ± 1.7),the Endoscopy score was(6.4±2.0),the CT score was(11.7±3.8).Our results of Real-time PCR and ELISA analysis showed that IL-35 mRNA and protein expression was significantly decreased in CRSwNP compared with normal nasal mucosa (P<0.05).But IL-17 and IL-10 were significantly increased by ELISA in CRSwNP compared with normal nasal mucosa (P<0.05).Conclusion: These data suggest that IL-35 may play an important role in the development and progression of CRSwNP.

Advances in the mechanism of IL-35 regulating the development of malignant tumors / 中国肿瘤临床

Interleukin-35 (IL-35) produced by regulatory T cells is a newly discovered inhibitory cytokine. It's a heterodimer consisting of IL-27βchain Epstein-Barr virus-induced gene 3 and IL-12αchain p35. In recent years, many studies have found that T cells, B cells, and tumor cells can secrete IL-35, which has a major inhibitory effect on the immune system. IL-35 plays an important role in tumor im-mune evasion and promotion of tumor progression and metastasis, and is an important factor which promotes the occurrence and de-velopment of tumors. Reducing IL-35 secretion may improve disease control, and it is very important to make a thorough inquiry into the role of IL-35 in regulating the activities of tumor cells. This review summarizes the molecular structure, biological functions, and regulatory roles of IL-35 in the development of malignant tumors. It is hoped that it can provide a novel perspective on the judgment of tumor prognosis and tumor targeted molecular therapy in the future.

Study on the relationship between anti-inflammatory cytokine IL-35 and delayed renal graft function / 器官移植

Objective To investigate the relationship between the interleukin (IL)-35 and the recovery of renal graft function. Methods Clinical data of 45 recipients receiving renal transplantation from donation after cardiac death (DCD) were retrospectively analyzed. According to the presence of delayed graft function (DGF) after renal transplantation, all recipients were divided into the immediate graft function (IGF) group (n=32) and DGF group (n=13). The serum creatinine (Scr) level and estimated glomerular filtration rate (eGFR) in the recipients were statistically compared between two groups at 1, 2, 3, 7, 14, 28 d and 3, 6 and 12 months after renal transplantation. The IL-35 levels in the serum and urine samples of the recipients were statistically compared between two groups at 1, 2, 3, 7, 14, 28 d following renal transplantation. Results In the DGF group, the renal function was restored slowly. Compared with the IGF group, the Scr level was significantly higher, whereas the eGFR was considerably lower in the DGF group at postoperative 7 d (both P<0.05). At 1 year after surgery, there was no significant difference in the Scr level between two groups. Compared with the IGF group, the eGFR in the DGF group was significantly lower at postoperative 1 year (P<0.05). At 1, 2, 3, 7, 14 d after operation, the serum levels of IL-35 in the DGF group were evidently lower than those in the IGF group (all P<0.05). Compared with the IGF group, the serum level of IL-35 in the DGF group was significantly increased at postoperative 28 d (P<0.05). At postoperative 1, 2, 3, 7 d, the IL-35 levels in the urine samples in the DGF group were significantly lower than those in the IGF group (all P<0.05). At postoperative 14 and 28 d, the IL-35 levels in the urine samples did not significantly differ between two groups (both P>0.05). Conclusions The low levels of IL-35 in the serum and urine of recipients after renal transplantation are associated with the incidence of DGF to certain extent, prompting that excessively weak systemic and local anti-inflammatory responses early after renal transplantation and uncontrolled excessive inflammatory response are probably the pivotal causes of DGF.

Regulatory T cells and asthma / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Asthma is a chronic disease of airway inflammation due to excessive T helper cell type 2 (Th2) response. Present treatment based on inhalation of synthetic glucocorticoids can only control Th2-driven chronic eosinophilic inflammation, but cannot change the immune tolerance of the body to external allergens. Regulatory T cells (Tregs) are the main negative regulatory cells of the immune response. Tregs play a great role in regulating allergic, autoimmune, graft-versus-host responses, and other immune responses. In this review, we will discuss the classification and biological characteristics, the established immunomodulatory mechanisms, and the characteristics of induced differentiation of Tregs. We will also discuss the progress of Tregs in the field of asthma. We believe that further studies on the regulatory mechanisms of Tregs will provide better treatments and control strategies for asthma.

Expression and role of interleukin 35-producing B cells and interleukin 35 from peripheral blood of patients with chronic hepatitis B / 中华传染病杂志

Objective To explore the level of interleukin 35-producing B cells (i35-Breg) as well as its effect factors,interleukin-35 (IL-35),in peripheral blood of patients with chronic hepatitis B (CHB),and their relationship with hepatitis B virus (HBV) DNA and liver inflammatory degree.Methods A total of 35 treatment-naive CHB patients,17 interferon (IFN)-treated HBeAg-positive CHB patients and 15 healthy controls (HC) were enrolled.The levels of i35-Breg and IL-35 in peripheral blood were tested by flow cytometry and enzyme-linked immunosorption assay (ELISA).Kruskal-Wallis test,Wilcox rank sum test and two variables correlation analysis were used for statistical analysis.Results The percentage of i35-Breg cells as well as IL-35 level in peripheral blood of naive CHB patients were 3.05％ (0.89％,4.97％) and 2.81 μg/L (0.30 μg/L,12.33 μg/L),respectively,which were both significantly higher than those in HC group,which were 0.17％ (0.13％,0.45％) and 0.17 μg/L(0,1.93 μg/L),respectively.The difference were statistical significant (Z=-3.309 and-2.419,respectively,P=0.001 and 0.016,respectively).The peripheral level of i35-Breg was negatively correlated with the viral load in treatment-naive CHB patients (r=-0.529,P=0.008),while there was no correlation between the peripheral level of IL-35 and the viral load in treatment-naive CHB patients (r=0.11,P=0.54).The levels of i35-Breg and IL-35 in HBeAg positive CHB patients were 3.16％ (1.34％,5.62％) and 4.58μg/L (0.79μg/L,22.37 μg/L),respectively,which were both higher than those in HC group.The difference was statistically significant (F=3.39 and 3.37,respectively,both P＜0.01).Compared to HC group,the IL-35 levels in peripheral blood of CHB patients with ALT and AST levels less than 300 U/L were 3.03 μg/L (0.74 μg/L,22.37 μg/L) and 3.25 μg/L (0.83 μg/L,22.35 μg/L),respectively,with statistically significant difference (F=2.868 and 3.114,respectively,both P＜0.01).Compared to HC group,the peripheral level of i35-Breg in treatment-naive CHB patients with ALT levels less than 300 U/L was 3.14％ (1.03％,4.65％),with statistically significant difference (F=3.219,P=0.004).The IL-35 level showed a decreased trend in CHB who received IFN therapy,but there was no statistically significant difference (x2 =1.45,P =0.48).Furthermore,the baseline IL-35 level in patients who developed sustained viral response (SVR) was 0 (0,13.33 g/L),which was lower than that in patients who developed partial or primary no response 0.61 μg/L (0,24.72 μg/L).However,there was no statistical difference (F=0.75,P =0.68).Conclusions i35-Breg as well as its effect factor,IL-35,are involved in the progression of chronic HBV infection.The percentage of i35-Breg cells as well as IL-35 level in peripheral blood of treatment-naive CHB patients are increased.The peripheral level of i35-Breg is negatively correlated with the viral load,while there is no correlation between the peripheral level of IL-35 and the viral load.The percentage of i35-Breg cells as well as IL-35 level in CHB patients with low inflammatory degree are increased.

Inhibitive effect of IL-35 on cardiac allograft rejection in mice / 中华器官移植杂志

Objective To investigate the action mechanism of IL-35 gene transfection ameliorating cardiac allograft rejection and prolonging allograft survival.Methods pEBI3-L-p35-Fc plasmid was amplified by polymerase chain reaction.In vitro plasmid DNA pEBI3-L-p35-Fc or pSec-L-Fc was,respectively,transfected into HEK293 cells using Lipofectamine 3000.At 48 and 72 h after transfection,IL-35 concentration in culture supernatant of transfected HEK293 cells was detected by ELISA.Balb/c and C57BL/6 splenocytes treated with mitomycin (MMC) served as the stimulators,those not treated with MMC as responders,and they were subjected to one-way mixed lymphocyte culture (MLC).In the presence or absence of IL-35,the percentage of CD4+ CD25+ Tregs was detected by flow cytometry.Abdominal heterotopic heart transplantation model was established by using inbred male Balb/c mice as donors and C57BL/6 as recipients respectively.In experimental group,recipients were intravenously administrated with IL-35 plasmid (50μg) on the day 1 to day 3 post-transplantation.The control mice were treated with normal saline.The IL-35 expression in the blood,CD4+ CD25+ Tregs proportion in the blood and spleen,and the survival and the histopathologic changes of the cardiac grafts were also observed.Results In vitro the transfected HEK293 cells expressed IL-35.IL-35 enhanced the proliferation of CD4+ CD25+ Tregs of MLC in vitro.The median survival time of the cardiac grafts in experimental group (16 days) was significantly longer than in control group (7 days) (P＜0.01).As compared with control group,CD4+ CD25+ Tregs proportion was significantly increased (P＜0.01),CD8+ T cells proportion was decreased (P＜0.01) and the proliferation of lymphocytes and monocytes infiltration was inhibited in the experimental group.Conclusion IL-35 could alleviate cardiac allograft rejection and prolong cardiac allograft survival via the induction of proliferation and differentiation of CD4+ CD25+ Tregs and inhibition of proliferation of CD8 + effector T cells.

Mechanism of IL-35 inhibition of inflammatory response and T cell response in alleviate of allergic rhinitis / 中国免疫学杂志

Objective:To investigate the effect of IL-35 on inflammatory response and T cell response in allergic rhinitis.Methods: 37 patients(observation group) with allergic rhinitis and 35 healthy volunteers(control group) after allergen detection of allergic rhinitisin in our hospital from Jan 2012 to Jan 2016 were selected as study subjects.The peripheral blood of observation group and control group were collected,and the serum levels of IL-35 were detected by ELISA.The animal model of allergic rhinitis in mice was established,the peripheral blood of mice was collected,and the serum level of IL-35 and IgE were detected by ELISA.The eosinophils that infiltrated in nasal mucosa were detected after tissue biopsy in mice.The mouse spleen cells were isolated and the ovalbumin antigen was added in the culture medium,IL-35 was or was not added into the culture medium,the ovalbumin specific T cell responses was detected.The cytokines IL-2,IL-4,IL-5,IL-10,IL-13,IL-17,IL-23,IL-27 and TNF-α in culture supernatant of ovalbumin specific T cells were detected by ELISA.The expression of IL-2,IL-4,IL-5,IL-10,IL-13,IL-17,IL-23,IL-27 and TNF-α in ovalbumin specific T cells were detected by Real-time PCR.The activation of JNK,Erk1/2 and p38 signal pathway in ovalbumin specific T cells were detected by Western blot.Results: The serum level of IL-35 in observation group was significantly lower than control group(P<0.05).The results showed that the number of eosinophils which infiltrated in AR mice nasal mucosa was significantly higher than normal mice(P<0.05),while the serum level of IL-35 in AR mice was significantly lower than normal mice(P<0.05).Ovalbumin specific T cell reactivity assay showed that IL-35 could significantly inhibit the T cell response.ELISA and Real-time PCR results showed that IL-35 could significantly down regulate the expression of IL-4,IL-5,IL-13,IL-17,IL-23 and TNF-α,and up regulate the expression of IL-2,IL-10 and IL-27.The Western blot results showed that IL-35 can inhibit the activation of JNK,Erk1/2 and p38 signal pathway of ovalbumin specific T in cells.Conclusion: IL-35 can regulate the expression of inflammatory cytokines in inflammatory response and inhibit T cell response,thus reducing allergic rhinitis,the mechanism may be through regulation of JNK,Erk1/2 and p38 signal pathway activation.

Expression level and clinical significance of IL-35 in maternal serum during pregnancy / 中华微生物学和免疫学杂志

Objective To analyze the levels of IL-35, IL-10 and TGF-β in women with or without pregnancy and to investigate the correlation between IL-35 and recurrent spontaneous abortion.MethodsLevels of IL-35, IL-10 and TGF-β in serum were analyzed by enzyme-linked immunosorbent assay (ELISA) in 120 gravidas with normal pregnancy, 40 gravidas with a history of recurrent spontaneous abortion, 40 healthy postpartum women and 40 healthy non-pregnant women of childbearing age.Single factor logistic regression analysis was used for correlation analysis.Results The level of serum IL-35 in normal pregnancies was significantly higher than that in non-pregnant women [333.6 (59.32, 1 391) pg/ml vs 123.9 (8.763, 471.7) pg/ml, P0.05].The level of serum IL-35 in gravidas with recurrent spontaneous abortion was significantly lower than that in healthy gravidas in their first trimester [220.4 (4.951, 702.0) pg/ml vs 386.5 (64.37, 1 355) pg/ml, P<0.05].Serum IL-35 was negatively correlated with the occurrence of recurrent spontaneous abortion (regression coefficient=-0.003, OR=0.997).Conclusion The level of serum IL-35 increases in healthy gravidas, but decreases in gravidas with recurrent spontaneous abortion.IL-35, rather than IL-10 or TGF-β, is recognized as an active player in maternal-fetal immune tolerance.

Changes in inducible IL-35-producing regulatory T cells in children with acute Kawasaki disease and their significance / 中华实用儿科临床杂志

Objective To investigate the changes and significances of inducible IL-35-producing regulatory T cells(iTR35) in immunological pathogcnesis of Kawasaki disease (KD).Methods Forty-eight children with KD and 32 age-matched healthy children (healthy control group) consented to participate in this study.Flow cytometry was performed to evaluate the proportions of CD4+ FOXP3-IL-12p35+IL-27EBI3+iTR35 and CD4+CD25high FOXP3+regulatory T cells (Treg),and expression levels of associated molecules such as programmed death-ligand 1 (PD-L1),CD169,programmed death 1 (PD-1),CD43,IL-12p35,Epstein-Barr virus induced 3 (IL-27EBI3),glycoprotein 130(gp130),IL-12 receptor beta 2 (IL-12Rβ2),phosphated signal transducer and activator of transcription 1 (pSTAT1) and phosphated signal transducer and activator of transcription 4 (pSTAT4).Transcription levels of the Sre homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2),phosphatase and tensin homolog (PTEN),Vavl guanine nucleotide exchange factor(Vav) in CD4+T cells were determined by quantitative real-time PCR.Plasma concentrations of IL-35,IL-10,TNF-α and IL-12 were measured by enzyme-linked immunosorbent assay.Results (1) The proportions of iTR35 and its expressions of IL-12p35 and IL-27EBI3 in patients with acute KD dccreased remarkably[iTR35:(0.72±0.26) ‰ vs (1.65±0.43) ‰,P＜0.05],and restored after treatment [iTR35:(1.58±0.63) ‰ vs (0.72±0.26) ‰,P＜0.05].(2) The proportions of Treg and transcriptional levels of IL-12p35 and IL-27EBI3 were down-regulated during acute phase of KD [Treg:(3.26±1.21) ％ vs (7.26±2.86) ％,P＜0.05],and increased to some extent after therapy [Treg:(5.89±2.60)％ vs (3.26±1.21)％,P＜0.05].Meanwhile,plasma concentrations of IL-35 and IL-10,and expressions of gp130,IL-12Rβ2,pSTAT1 and pSTAT4 in iTR35 of patients with acute KD were found lower than those of the healthy control group (all P＜0.05),and increased after treatment (P＜0.05).Additionally,positive correlations were found between plasma concentrations of IL-35 and the proportion of iTR35 or its expressions of IL-12p35 and IL-27EBI3,respectively.(3) Expressions of PD-L1 and CD169 on CD14 + cells and plasma concentrations of TNF-α and IL-12 were elevated significantly during acute KD(all P＜0.05),as well as expression levels of the ligands (PD-1 and CD43) and its downstream molecules (SHP-2,PTEN,Vav) in CD4 + T cells were found to be lower in patients with acute KD (P＜0.05),and restored remarkably after therapy.Conclusion Insufficiency of iTR35 and its expression of IL-35 might be one of the important factors contributing to immunological dysfunction in KD.

Effect of sodium selenite on Treg cells in peripheral blood mononuclear cells in patients with Graves disease / 中国免疫学杂志

Objective:Recently,selenium was used for the treatment of Graves disease. However,there has been no reports that selenium affected the immune function of Graves disease at the cellular level so far. It is reported the effect of sodium selenite on Treg cells in peripheral blood mononuclear cells in patients with Graves disease in the present study. Methods:AFS were used to detect the level of serum selenium;PBMC( Peripheral blood mononuclear cells) were extracted,then,cultured with sodium selenite. Foxp3 mRNA expression was tested by Real-time fluorescence PCR,and ELISA was used to detect the secretion of IL-35. Results:The serum sodium selenite levels of GD group are significantly lower than the HC group;The expression of Foxp3 mRNA and secretion of IL-35 are both increased. Conclusion:It shows sodium selenite could improve the state of immune disorders by recovering the function of Treg cells.

Role of IL-12 family in autoimmune diseases / 军事医学

The interleukin-12 (IL-12) family, including IL-12, IL-23, IL-27,and IL-35, is characterized by unique structures and molecular partners.This is the only family of heterodimeric cytokines, which endows them with a unique set of connections and functional interactions.They not only play an important role in the regulation of inflammation, but are closely related to various autoimmune diseases.Here we discuss the structural aspects of these cytokines and their effect on some autoimmune diseases.

Review the Function and Structure of Interleukin-35 and Its Function in Mediating Treg Cell Immuno-Suppression / 天津医药

Interleukin (IL)-35 is a new member of IL-12 family who is secreted by T regulatory cells to strongly sup?press immuno reaction directly or indirectly. There is a growing interest in the using IL-35 as a potential therapy for chronic in?flammatory , cancer and autoimmune diseases. Here we reviewed IL-35 and its function as a mediator of suppression.

Interleukin (IL)-35 is raising our expectations / Las expectativas futuras de la interleukina (IL)-35

Purpose: To elucidate and discuss the role of IL-35 in immunity to parasitic and bacterial infections as well as in autoimmunity in terms of its anti-infammatory properties, we highlight significant findings on this novel member of the IL-12 family. Methods: Studies using genetically defcient mice have greatly enhanced our understanding of the biology of IL-35. On the basis of data derived from the analysis of these genetically deficient mice published by NIH, we focus on the key features of this heterodimeric cytokine, especially its relation to the other IL-12 family members, and discuss its potential relevance to the clinical usage. Principal fndings: IL-35 is required for the CD4+CD25+ Treg cells-mediated immune regulation, the alleviation of some inflammatory responses, as well as the expansion of CD4+CD25- Teff cells simultaneously. Moreover, administration or augmentation of IL-35 suppresses some diseases of autoimmune or allergic origin like collagen-induced arthritis or Helicobacter- induced colitis in animal models, demonstrating its potential in therapy of diseases mediated by inflammatory cytokines. However, some questions involving it are still unclear, including the composition of IL-35 receptor, IL-35-related cell signaling pathway, the different expression patterns of IL-35 between human and murine T cells, etc. Conclusion: As our understanding of the IL-35 is rapidly growing and changing, it will bring us more therapeutic strategies towards some intractable immune diseases such as Lupus Erythematosus.

Esta es una revisión acerca del rol de IL-35, un nuevo miembro de la familia IL-12, en la respuesta inmunitaria contra infecciones parasitarias y bacterianas y de su rol benefcioso en reacciones auto inmunes, debido sus propiedades antiinfamatorias. Basándose en estudios de ratones genéticamente defcientes se ha determinado que se requiere IL-35 para la acción inmunoreguladora de las células T reguladoras CD4+CD25+, para mitigar algunos procesos inflamatorios y para expandir simultáneamente los clones de células T efectoras CD4+CD25-. Mas aún, la administración o estimulación de la acción de IL-35 en modelos animales, suprime algunas enfermedades de origen alérgico o autoinmune tales como la colitis colágena y la colitis inducida por Helicobacter. Estos experimentos demuestran el potencial terapéutico de IL-35 en enfermedades mediadas por citokinas inflamatorias. Sin embargo, algunos aspectos de la citokina aún no han sido dilucidados, tales como la composición del receptor de IL-35, la vía de señalización celular asociada a IL-35 y los diversos patrones de expresión de la citokina en células humanas y de ratones. En la medida que aumente el conocimiento acerca de las acciones de IL-35, nos podrá proveer tratamientos para algunas enfermedades auto inmunes actualmente limitadas en su tratamiento, como el lupus eritematoso.