Interleukin-35 on B cell and T cell induction and regulation

Huang, Ai; Cheng, Lin; He, Miao; Nie, Jing; Wang, Jianjun; Jiang, Ke

doi:10.1186/s12950-017-0164-5

Cited by 64 publications

(52 citation statements)

References 45 publications

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“…IL‐35 is identified as an anti‐inflammatory and immunosuppressive cytokine which is mainly produced by Treg cells . The results of the present study showed that the serum IL‐35 levels in PU patients were significantly decreased compared with AS and NHS groups.…”

Section: Discussionmentioning

confidence: 47%

“…IL‐35 has been described as a novel cytokine with anti‐inflammatory and immunomodulatory properties, constituted by the IL‐12p35 and Epstein‐Barr virus‐induced gene 3 (EBI3) subunits . It is produced by Treg cells and a particular CD4 + Treg cells subgroup, called IL‐35‐induced CD4 + Treg (iTr35) cells, because their proliferation is promoted precisely by IL‐35 . The IL‐35 receptor is composed of IL‐12Rβ2 and gp130, which are also associated with the IL‐12 and IL‐27 receptors, respectively .…”

Section: Introductionmentioning

confidence: 99%

“…It is produced by Treg cells and a particular CD4 + Treg cells subgroup, called IL‐35‐induced CD4 + Treg (iTr35) cells, because their proliferation is promoted precisely by IL‐35 . The IL‐35 receptor is composed of IL‐12Rβ2 and gp130, which are also associated with the IL‐12 and IL‐27 receptors, respectively . Anti‐inflammatory and immunosuppressive action of IL‐35 is exerted through the induction of Treg cells, the promotion of regulatory B cells, and the suppression of macrophages and effector T cells .…”

Section: Introductionmentioning

confidence: 99%

“…On the other side, IL‐35 can induce infectious persistence and increase in tumor progression . Indeed, a reduction in tumor growth has been obtained after blocking of IL‐35 in different animal models of human cancers, along with an increase in T‐cell proliferation and functions and responses toward specific antigens …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Diminished circulating concentration of interleukin‐35 in Helicobacter pylori‐infected patients with peptic ulcer: Its association with FOXP3 gene polymorphism, bacterial virulence factor CagA, and gender of patients

et al. 2018

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Section: Discussionmentioning

confidence: 47%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Diminished circulating concentration of interleukin‐35 in Helicobacter pylori‐infected patients with peptic ulcer: Its association with FOXP3 gene polymorphism, bacterial virulence factor CagA, and gender of patients

et al. 2018

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“…These properties make MSC as a promising potential treatment of autoimmune diseases. 1 Our previous studies have found that bone marrow-derived (BM)-MSC from systemic lupus erythematosus (SLE) patients are defective structurally and functionally, 2 treatment with modified and optimised MSC may bring a better effect on patients with autoimmune diseases. Most efforts have relied on adeno-and lentiviral vectors for delivering genes to MSC.…”

mentioning

confidence: 99%

AB0063 High-efficiency transduction of mesenchymal stem cells by aav2/dj vector for their potential use in autoimmune diseases

Zhang

Tang

Wang

et al. 2018

Cytokines and Inflammatory Mediators

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BackgroundMesenchymal stem cells (MSC), multipotential non-hematopoietic progenitors, can be isolated from various tissues and can modulate allogeneic immune cell responses. These properties make MSC as a promising potential treatment of autoimmune diseases.1 Our previous studies have found that bone marrow-derived (BM)-MSC from systemic lupus erythematosus (SLE) patients are defective structurally and functionally,2 treatment with modified and optimised MSC may bring a better effect on patients with autoimmune diseases. Most efforts have relied on adeno- and lentiviral vectors for delivering genes to MSC. Effective as these vectors may be, concerns regarding their immunogenicity and, in the case of lentivirus, the risk of insertional mutagenesis, have led to the pursuit of safer alternatives. Among these, adeno-associated virus (AAV) holds several advantages as a vector for human gene therapy. There are many serotypes of AAV available, and certain serotypes have been found to transduce specific cell types more efficiently than others.ObjectivesTo determine the efficiency of different serotypes of AAV vectors for their ability to mediate transduction of different sources of MSC and assess whether AAV transduction affects MSC multipotentiality.MethodsSerotypes 1, 2, 5, 6, 8, 9, PHP and DJ of AAV vectors were constructed in Viral Core, Boston Children’s Hospital. The enhanced green fluorescent protein (eGFP) gene under transcriptional control of a CAG promoter was cloned into the AAV vector backbone. MSC derived from umbilical cord (UC), BM and amniotic fluid (AF) were isolated and approximately 1 × 105 MSC were used for transductions with AAV vectors. eGFP expression was evaluated 3 days after transduction by fluorescence microscopy and flow cytometry. The capacity of MSC to differentiate in vitro was assessed.Abstract AB0063 – Figure 1A: the transduction efficiencies of AAVs (MOI=5:1) in AF-MSC, BM-MSC and UC-MSC, B: the transduction efficiencies of AAV/DJ in UC-MSC with different MOI.ResultsAAV serotype DJ vector was the most efficient in transducing MSC. AAV was added directly to the medium at 5 multiplicities of infection (MOI), 41% UC–MSC was transduced by AAV2/DJ, while the transfection is 0.47%, 0.3%, 10.5%, 0.3%, 1.84%, 0.06%, 0.16% by AAV2/1, AAV2/2, AAV2/5, AAC2/6, AAV2/8, AAV2/9, AAV2/PHP (Fig 1A). Transduction efficiencies ranged from 73.5% for MOI 10% to 91.3% for MOI 320 in UC–MSC (Fig 1B).MSC derived from different tissues share a comparable level of transduction with the same AAV vector serotype. In our result, AAV2/DJ was the most efficient in transducing UC–MSC and AF–MSC.AAV2/DJ transduced MSC retained the same multipotential activity to differentiate into osteogenic and adipogenic lineage as comparable to un–transduced cells.ConclusionsAAV2/DJ vector can be used as a highly efficient tool to modify MSC ex vivo for therapeutic transplantation for autoimmune diseases.References[1] Liang J, Wang D, Dominique F, Sun L. Mesenchymal stem cells for treating autoimmune diseases: The Chinese experience f...

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Decreased Expression of IL‐35 and Its Receptor Contributes to Impaired Megakaryopoiesis in the Pathogenesis of Immune Thrombocytopenia

Cai,

Gui,

et al. 2024

Advanced Science

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Recent findings have shown that the level of interleukin‐35 (IL‐35) is abnormal in several autoimmune diseases. Nonetheless, whether IL‐35 participates in the pathogenesis of immune thrombocytopenia (ITP) remains unclear. The current study investigates whether IL‐35 modulates megakaryopoiesis. The results show that IL‐35 receptors are progressively expressed on bone marrow megakaryocytes during the in vitro differentiation of CD34+ progenitors. IL‐35 increases the number of megakaryocyte colony‐forming units through the Akt pathway. The level of bone marrow IL‐35 is reduced in ITP patients, and the decreased level of IL‐35 may inhibit megakaryopoiesis. Then, the potential causes of decreased IL‐35 in ITP patients are explored. The primary type of cell that secretes IL‐35, known as IL‐35‐producing regulatory T cells (iTr35), is reduced in ITP patients. Bone marrow mesenchymal stem cells (MSCs) from ITP patients exhibit an impaired capability of inducing iTr35 due to enhanced apoptosis, which may contribute to the reduced level of bone marrow IL‐35 in ITP patients. Iguratimod promotes megakaryocyte development and differentiation by elevating the expression of IL‐35 receptors on megakaryocytes. Iguratimod improves response rates and reduces bleeding symptoms in corticosteroid‐resistant ITP patients.

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Interleukin-35 on B cell and T cell induction and regulation

Cited by 64 publications

References 45 publications

Diminished circulating concentration of interleukin‐35 in Helicobacter pylori‐infected patients with peptic ulcer: Its association with FOXP3 gene polymorphism, bacterial virulence factor CagA, and gender of patients

Diminished circulating concentration of interleukin‐35 in Helicobacter pylori‐infected patients with peptic ulcer: Its association with FOXP3 gene polymorphism, bacterial virulence factor CagA, and gender of patients

AB0063 High-efficiency transduction of mesenchymal stem cells by aav2/dj vector for their potential use in autoimmune diseases

Decreased Expression of IL‐35 and Its Receptor Contributes to Impaired Megakaryopoiesis in the Pathogenesis of Immune Thrombocytopenia

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