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https://www.readbyqxmd.com/read/29141218/reciprocal-expression-of-il-35-and-il-10-defines-two-distinct-effector-treg-subsets-that-are-required-for-maintenance-of-immune-tolerance
#1
Xundong Wei, Jianhua Zhang, Qianchong Gu, Man Huang, Wei Zhang, Jie Guo, Xuyu Zhou
Regulatory T cells (Tregs) can exert their functions through multiple suppressive mechanisms; however, it is unclear how Tregs exactly employ these mechanisms. In this study, we found that interleukin-35 (IL-35)-producing Tregs were a distinct effector population from the IL-10-producing subset. We also revealed that these two subsets of effector Tregs have different transcription factor dependency. Terminal differentiation regulator Blimp1 was only critical for IL-10 production, but not for IL-35; Foxp3 was essential for IL-35 but dispensable for IL-10 production...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29123149/il-6-il-12-cytokine-receptor-shuffling-of-extra-and-intracellular-domains-reveals-canonical-stat-activation-via-synthetic-il-35-and-il-39-signaling
#2
D M Floss, M Schönberg, M Franke, F C Horstmeier, E Engelowski, A Schneider, E M Rosenfeldt, J Scheller
IL-35 and IL-39 are recently discovered shared members of the IL-6- and IL-12-type cytokine family with immune-suppressive capacity. IL-35 has been reported to induce the formation of four different receptor complexes: gp130:IL-12β2, gp130:gp130, IL-12β2:IL-12β2, and IL-12β2:WSX-1. IL-39 was proposed to form a gp130:IL-23R receptor complex. IL-35, but not IL-39, has been reported to activate non-conventional STAT signaling, depending on the receptor complex and target cell. Analyses of IL-35 and IL-39 are, however, hampered by the lack of biologically active recombinant IL-35 and IL-39 proteins...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29083399/oxidative-stress-controls-regulatory-t-cell-apoptosis-and-suppressor-activity-and-pd-l1-blockade-resistance-in-tumor
#3
Tomasz Maj, Wei Wang, Joel Crespo, Hongjuan Zhang, Weimin Wang, Shuang Wei, Lili Zhao, Linda Vatan, Irene Shao, Wojciech Szeliga, Costas Lyssiotis, J Rebecca Liu, Ilona Kryczek, Weiping Zou
Live regulatory T cells (Treg cells) suppress antitumor immunity, but how Treg cells behave in the metabolically abnormal tumor microenvironment remains unknown. Here we show that tumor Treg cells undergo apoptosis, and such apoptotic Treg cells abolish spontaneous and PD-L1-blockade-mediated antitumor T cell immunity. Biochemical and functional analyses show that adenosine, but not typical suppressive factors such as PD-L1, CTLA-4, TGF-β, IL-35, and IL-10, contributes to apoptotic Treg-cell-mediated immunosuppression...
October 30, 2017: Nature Immunology
https://www.readbyqxmd.com/read/29074035/the-il-12-cytokine-family-in-cardiovascular-diseases
#4
T van der Heijden, I Bot, J Kuiper
Cytokines of the Interleukin (IL)-12 family, consisting of IL-12, IL-23, IL-27 and IL-35, are important regulators in (chronic) inflammatory disorders such as rheumatoid arthritis and multiple sclerosis, but also in cardiovascular diseases. Cytokines of the IL-12 family consist of two subunits and are known for their regulatory functions in the immunologic response, more specifically in the regulation and differentiation of T-helper (Th) cells such as Th1 and Th17 cells. Binding of these cytokines to its specific heterodimeric receptor results in the activation of the JAK-STAT signaling...
October 23, 2017: Cytokine
https://www.readbyqxmd.com/read/29070122/-levels-of-t-lymphocyte-subsets-il-17-il-35-and-ifn-%C3%AE-in-peripheral-blood-and-their-clinical-significance-in-patients-with-multiple-myeloma
#5
Zhao-Juan Xu, Dong Zhao, Fu-Ping Li, Ying-Fang Wang, Hui-Ying Xiao, Xu Wang
OBJECTIVE: To explore the levels of T-lymphocyte subsets and IL-17, IL-35, IFN-γ in peripheral blood of patients with multiple myeloma(MM) and their clinical significance. METHODS: A total of 86 MM patients in our hospital from January 2014 to January 2017 were enrolled in MM group and 30 healthy persons were enrolled in control group, the CD4(+)/CD8(+) T cells ratio, CD4(+)CD25(high/+) CD127(low/-) Treg level in peripheral blood were detected by flow cytometer...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29069729/interleukin-35-expression-is-associated-with-colon-cancer-progression
#6
Jian Zhang, Tao Mao, Shuyun Wang, Dongsheng Wang, Zhaojian Niu, Zhenqing Sun, Jianli Zhang
Colon cancer development is closely related to inflammation. Thus, we conducted the present investigation to study the effects of IL-35 (Interleukin 35), a newly identified anti-inflammatory factor, on colon cancer development. We first evaluated the IL-35 expression in 186 pairs of colon cancer samples and paired adjacent normal tissues by qPCR, ELISA (Enzyme-linked immunoassay) and tissue microarrays. Then the role of IL-35 on patient survival rates, colon cancer progression and their sensitivity to chemotherapy drugs were assessed...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29054723/aberrant-frequency-of-il-35-producing-b-cells-in-colorectal-cancer-patients
#7
Ke Wang, Hui Gong, Rui Chai, Hang Yuan, Yanxia Chen, Jinlin Liu
BACKGROUND: The IL-10 dependent regulatory function of B cells had recently more and more investigated and play important roles in cancer immunity, however, beyond IL-10 whether other inhibitory cytokines play an important role in cancer is lacking. Here, we investigated the role of IL-35 producing B cells in colorectal cancer (CRC). METHODS: Thirty-two healthy controls (HC) and 49 untreated CRC patients were enrolled and the IL-35 producing B cells in the peripheral blood were investigated...
October 17, 2017: Cytokine
https://www.readbyqxmd.com/read/29054137/il-35-gene-modified-mesenchymal-stem-cells-protect-the-con-a-induced-fulminant-hepatitis-through-decreasing-the-ifn-g-level
#8
Wei Wang, Hao Guo, Hongyue Li, Yongjia Yan, Chao Wu, Xiaodong Wang, Xianghui He, Na Zhao
Interleukin 35 (IL-35) is a relatively newly identified cytokine required for the regulatory and suppressive functions of regulatory T cells(Treg), playing an important role in the prevention of autoimmune diseases. In this study, we used the MSCs as the gene-delivery vehicles for IL-35 gene therapy and investigated their protective effects in Con A-induced autoimmune hepatitis. Results showed that IL-35 gene modified MSCs(IL-35-MSCs) can specifically migrate to the injured liver tissues and significantly narrow the necrosis areas and reduce the hepatocytes apoptosis...
October 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29051763/il-12p35-inhibits-neuroinflammation-and-ameliorates-autoimmune-encephalomyelitis
#9
Jin Kyeong Choi, Ivy M Dambuza, Chang He, Cheng-Rong Yu, Anita N Uche, Mary J Mattapallil, Rachel R Caspi, Charles E Egwuagu
Multiple sclerosis (MS) is an inflammatory demyelinating disease in which cytokines produced by immune cells that infiltrate the brain and spinal cord play a central role. We show here that the IL-12p35, the alpha subunit of IL-12 or IL-35 cytokine, might be an effective biologic for suppressing neuroinflammatory responses and ameliorating the pathology of experimental autoimmune encephalomyelitis (EAE), the mouse model of human MS. We further show that IL-12p35 conferred protection from neuropathy by inhibiting the expansion of pathogenic Th17 and Th1 cells and inhibiting trafficking of inflammatory cells into the brain and spinal cord...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28989066/interleukin-35-expression-correlates-with-microvessel-density-in-pancreatic-ductal-adenocarcinoma-recruits-monocytes-and-promotes-growth-and-angiogenesis-of-xenograft-tumors-in-mice
#10
Chongbiao Huang, Zengxun Li, Na Li, Yang Li, Antao Chang, Tiansuo Zhao, Xiuchao Wang, Hongwei Wang, Song Gao, Shengyu Yang, Jihui Hao, He Ren
BACKGROUND & AIMS: Cells of the monocyte lineage contribute to tumor angiogenesis. Interleukin 35 (IL35) is a member of the IL12 family produced by regulatory, but not effector, T cells. IL35 is a dimer comprising the IL12 alpha and IL27 beta chains, encoded by IL12A and EBI3, respectively. Expression of IL35 is increased in pancreatic ductal adenocarcinomas (PDACs) compared with normal pancreatic tissues, and promotes metastasis. We investigated the role of IL-35 in monocyte-induced angiogenesis of PDAC in mice...
October 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28959012/il-12p35-induces-expansion-of-il-10-and-il-35-expressing-regulatory-b-cells-and-ameliorates-autoimmune-disease
#11
Ivy M Dambuza, Chang He, Jin Kyeong Choi, Cheng-Rong Yu, Renxi Wang, Mary J Mattapallil, Paul T Wingfield, Rachel R Caspi, Charles E Egwuagu
Interleukin 35 (IL-35) is a heterodimeric cytokine composed of IL-12p35 and Ebi3 subunits. IL-35 suppresses autoimmune diseases while preventing host defense to infection and promoting tumor growth and metastasis by converting resting B and T cells into IL-10-producing and IL-35-producing regulatory B (Breg) and T (Treg) cells. Despite sharing the IL-12p35 subunit, IL-12 (IL-12p35/IL-12p40) promotes inflammatory responses whereas IL-35 (IL-12p35/Ebi3) induces regulatory responses, suggesting that IL-12p35 may have unknown intrinsic immune-regulatory functions regulated by its heterodimeric partner...
September 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/28957824/the-role-of-regulatory-b-cells-in-allergen-immunotherapy
#12
Willem van de Veen
PURPOSE OF REVIEW: Allergen immunotherapy (AIT) is currently the only curative treatment available for allergic diseases, and has been used in clinical practice for over a century. Induction and maintenance of immune tolerance to nonhazardous environmental and self-antigens is essential to maintain homeostasis and prevent chronic inflammation. Regulatory B (BREG) cells are immunoregulatory cells that protect against chronic inflammatory responses primarily through production of anti-inflammatory cytokines such as IL-10, transforming growth factor-β, and IL-35...
December 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28936965/-important-role-of-interleukin-35-in-infectious-diseases-and-its-significance
#13
Renqi Yao, Yao Wu, Bing Ma
Infectious diseases are resulted from the invasion of an organism's body tissues by multiple disease-causing agents. It has been demonstrated that the occurrence and development of infectious diseases are closely associated with the functional status of immune system. Cytokines play significant roles in modulating the host immune response to the clearance of pathogenic microorganisms and maintaining immune homeostasis. Interleukin-35 (IL-35), as a newly identified member of IL-12 family, exerts suppressive effect on immune response by means of a specific pattern...
September 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28916184/role-of-the-il-12-il-35-balance-in-sj%C3%A3-gren-s-syndrome
#14
Olivier Fogel, Elodie Rivière, Raphaèle Seror, Gaetane Nocturne, Saida Boudaoud, Bineta Ly, Jacques-Eric Gottenberg, Véronique Le Guern, Jean-Jacques Dubost, Joanne Nititham, Kimberly E Taylor, Philippe Chanson, Philippe Dieudé, Lindsey A Criswell, Bernd Jagla, Alice Thai, Michael Mingueneau, Xavier Mariette, Corinne Miceli-Richard
BACKGROUND: An interferon (IFN) signature is involved in the pathogenesis of primary Sjögren's syndrome (pSS), but whether the signature is type 1 or 2 remains controversial. Mouse models and genetic studies suggested the involvement of T helper 1 and type 2 IFN pathways. Likewise, polymorphisms of interleukin 12A gene (IL-12A), which encodes for IL-12p35, have been associated with pSS. IL-12p35 subunit is shared by 2 heterodimers, IL-12 and IL-35. OBJECTIVE: To confirm the genetic association of IL-12A polymorphism and pSS and elucidate the involvement of the IL-12/IL-35 balance in pSS by functional studies...
September 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28888053/mesenchymal-stem-cells-overexpressing-interleukin-35-propagate-immunosuppressive-effects-in-mice
#15
H Guo, N Zhao, H Gao, X He
To explore generation of interleukin (IL)-35-expressing mouse adipocyte-derived mesenchymal stem cells (Ad-MSCs) using lentiviral vector and their potential immunosuppressive effects in mice. Ad-MSCs were isolated and cultured in vitro and transfected with a lentivirus vector for overexpression of the therapeutic murine IL-35 gene. IL-35 expression in transfected MSCs (IL-35-MSCs) was quantified by enzyme-linked immunosorbent assay (ELISA). The lymphocytes subsets after one-way mixed lymphocyte culture and in vivo intravenous transplantation were analysed by flow cytometry to evaluate the immunosuppressive effects of IL-35-MSCs...
November 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28844943/the-unknown-aspect-of-baff-inducing-il-35-production-by-a-cd5-cd1d-hi-fc%C3%AE-riib-hi-regulatory-b-cell-subset-in-lupus
#16
Yamin Zhang, Jun Li, Nuoya Zhou, Yi Zhang, Min Wu, Jian Xu, Chen Shen, Xiangjie An, Guanxin Shen, Ming Yang, Chun Zhang, Juan Tao
IL-35 is a critical immunosuppressive cytokine that plays an important role in various autoimmune diseases. The purpose of this study was to determine whether BAFF, a key pathogenic factor in systemic lupus erythematosus, also a dichotomous regulator for B-cell immune responses, has an effect on IL-35-producing regulatory B cells and their underlying mechanisms in lupus. We found that exogenous BAFF could induce IL-35 production by splenic B cells from MRL-Fas(lpr/lpr) mice. BAFF-induced IL-35-producing B cells were mainly from the marginal zone B-cell subset and exhibited a CD5(+)CD1d(hi)FcγRIIb(hi) phenotype...
August 24, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28833201/dynamics-of-regulatory-t-cells-tregs-in-patients-with-oral-squamous-cell-carcinoma
#17
Sadhna Aggarwal, Suresh C Sharma, Satya N Das
BACKGROUND AND OBJECTIVES: The immune dysfunction in oral squamous cell carcinoma (OSCC) patients is one of the major factors for growth and dissemination of tumor affecting disease-free survival. METHODS: The phenotypic and functional characteristics of Regulatory T (Treg ) CD4(+) CD25(+) FoxP3(+) subsets in OSCC patients were assessed by multicolor flow cytometry and its effector component (TGF-β) by Western blot and qRT-PCR. RESULTS: An increased (P < 0...
August 22, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28794689/interleukin-35-on-b-cell-and-t-cell-induction-and-regulation
#18
REVIEW
Ai Huang, Lin Cheng, Miao He, Jun Nie, Jianjun Wang, Ke Jiang
Interleukin (IL)-35 is a relatively newly discovered member of IL-12 cytokine family that is unique in that it is a dimer formed by two subunits. The review documents the structure, secretion and signal transduction of IL-35, the regulation effect of IL-35 on B cells and T cells as well as the adoptive transfer of IL-35+ regulatory B cells (Breg), therapeutic prospects of recombinant IL-35 (rIL-35) and IL-35 regulation role in various diseases. B-cell regulation expands the regulatory range of IL-35 and alters the view that IL-10 is the chief immune mechanism for Breg cells which secrete IL-35...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28791821/il-22-modulates-inflammatory-properties-of-human-primary-aortic-smooth-muscle-cells
#19
Paulina Gorzelak-Pabis, Maciej Chałubiński, Katarzyna Wojdan, Emilia Łuczak, Maciej Borowiec, Marlena Broncel
BACKGROUND: IL-22 is expressed at barrier surfaces, which suggests its critical role in the maintenance of normal barrier homeostasis and tissue repair. IL-22 can both promote pathological inflammation and prevent the destruction of tissues. The functional outcomes of IL-22 on vascular smooth muscle cells, which are shown to regulate immune processes within the vascular wall and which are involved in certain pathologies, have not been analyzed. OBJECTIVES: The effect of IL-22 on the expression of novel antiand pro-inflammatory and barrier disrupting cytokines, apoptosis and the expression of adhesive molecules in human primary aortic smooth muscle cells (AoSMC) was investigated...
May 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/28791025/the-ido-ahr-axis-controls-th17-treg-immunity-in-a-pulmonary-model-of-fungal-infection
#20
Eliseu Frank de Araújo, Claudia Feriotti, Nayane Alves de Lima Galdino, Nycolas Willian Preite, Vera Lúcia Garcia Calich, Flávio Vieira Loures
In infectious diseases, the enzyme indoleamine 2,3 dioxygenase-1 (IDO1) that catalyzes the tryptophan (Trp) degradation along the kynurenines (Kyn) pathway has two main functions, the control of pathogen growth by reducing available Trp and immune regulation mediated by the Kyn-mediated expansion of regulatory T (Treg) cells via aryl hydrocarbon receptor (AhR). In pulmonary paracoccidioidomycosis (PCM) caused by the dimorphic fungus Paracoccidioides brasiliensis, IDO1 was shown to control the disease severity of both resistant and susceptible mice to the infection; however, only in resistant mice, IDO1 is induced by TGF-β signaling that confers a stable tolerogenic phenotype to dendritic cells (DCs)...
2017: Frontiers in Immunology
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