Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Inflammation
Published in: Journal of Inflammation 1/2017

Open Access 01-12-2017 | Review

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

Authors: Ai Huang, Lin Cheng, Miao He, Jun Nie, Jianjun Wang, Ke Jiang

Published in: Journal of Inflammation | Issue 1/2017

Login to get access

Abstract

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. IL-35 induces Breg cells, which then can induce Treg cells. IL-35 also plays an immunomodulatory role in the human body.
Literature
1.
Niedbala W, Wei XQ, Cai B, Hueber AJ, Leung BP, IB MI. IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. Eur J Immunol. 2007;37:3021–9.CrossRefPubMed
2.
Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM, et al. The inhibitory cytokine IL- 35 contributes to regulatory T- cell function. Nature. 2007;450:566–9.CrossRefPubMed
3.
Tedder TF, Leonard WJ. Autoimmunity:regulatory B cells—IL-35 and IL-21regulate the regulators. Nat Rev Rheumatol. 2014;10:452–3.CrossRefPubMed
4.
Ma X, Trinchieri G. Regulation of interleukin-12 production in antigen-presenting cells. Adv Immunol. 2001;79:55–92.CrossRefPubMed
5.
O’Shea JJ, Paul WE. Regulation of T (H) 1 differentiation—controlling the controllers. Nat Immunol. 2002;3:506–8.CrossRefPubMed
6.
Hunter CA. New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions. Nat Rev Immunol. 2005;5:521–31.CrossRefPubMed
7.
Wang RX, Yu CR, Dambuza IM, Mahdi RM, Dolinska MB, Sergeev YV, et al. Interleukin-35 induces regulatory B cells that suppress autoimmune disease. Nat Med. 2014;20:633–41.CrossRefPubMedCentralPubMed
8.
Shen P, Roch T, Lampropoulou V, O'Connor RA, Stervbo U, Hilgenberg E, et al. IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. Nature. 2014;507:366–70.CrossRefPubMedCentralPubMed
9.
Collison LW, Delgoffe GM, Guy CS, Vignali KM, Chaturvedi V, Fairweather D, et al. The composition and signaling of the IL-35 receptor are unconventional. Nat Immunol. 2012;13:290–9.CrossRefPubMedCentralPubMed
10.
Yanaba K, Bouaziz JD, Haas KM, Poe JC, Fujimoto M, Tedder TF, et al. A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity. 2008;28:639–50.CrossRefPubMed
11.
Neves P, Lampropoulou V, Calderon-Gomez E, Roch T, Stervbo U, Shen P, et al. Signaling via the MyD88 adaptor protein in B cells suppresses protective immunity during salmonella typhimurium infection. Immunity. 2010;33:777–90.CrossRefPubMed
12.
Evans JG, Chavez-Rueda KA, Eddaoudi A, Meyer-Bahlburg A, Rawlings DJ, Ehrenstein MR, et al. Novel suppressive function of transitional 2 B cells in experimental arthritis. J Immunol. 2007;178:7868–78.CrossRefPubMed
13.
Ding Q, Yeung M, Camirand G, Zeng Q, Akiba H, Yagita H, et al. Regulatory B cells are identified by expression of TIM-1 and can be induced through TIM-1 ligation to promote tolerance in mice. J Clin Invest. 2011;121:3645–56.CrossRefPubMedCentralPubMed
14.
Yoshizaki A, Miyagaki T, DiLillo DJ, Matsushita T, Horikawa M, Kountikov EI, et al. Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions. Nature. 2012;491:264–8.CrossRefPubMedCentralPubMed
15.
Wilson MS, Taylor MD, O'Gorman MT, Balic A, Barr TA, Filbey K, et al. Helminth-induced CD19+CD23hi B cells modulate experimental allergic and autoimmune inflammation. Eur J Immunol. 2010;40:1682–96.CrossRefPubMedCentralPubMed
16.
Wirtz S, Billmeier U, Mchedlidze T, Blumberg RS, Neurath MF. Interleukin-35 mediates mucosal immune responses that protect against T-cell-dependent colitis. Gastroenterology. 2011;141:1875–86.CrossRefPubMedCentralPubMed
17.
18.
Collison LW, Chaturvedi V, Henderson AL, Giacomin PR, Guy C, Bankoti J, et al. IL-35-mediated induction of a potent regulatory T cell population. Nat Immunol. 2010;11:1093–01.CrossRefPubMedCentralPubMed
19.
Presky DH, Yang H, Minetti LJ, Chua AO, Nabavi N, Wu CY, et al. A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits. Proc Natl Acad Sci U S A. 1996;93:14002–7.CrossRefPubMedCentralPubMed
20.
Canda-Sánchez A, Salgado FJ, Pérez-Díaz A, Varela-González C, Arias P, Nogueira M. Differential distribution of both IL-12Rbeta chains in the plasma membrane of human T cells. J Membr Biol. 2009;227:1–12.CrossRefPubMed
21.
Maldonado RA, Soriano MA, Perdomo LC, Sigrist K, Irvine DJ, Decker T, et al. Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse. J Exp Med. 2009;206:877–92.CrossRefPubMedCentralPubMed
22.
Devergne O, Birkenbach M, Kieff E. Epstein-Barr virus-induced gene 3 and the p35 subunit of interleukin 12 form a novel heterodimeric hematopoietin. Proc Natl Acad Sci U S A. 1997;94:12041–6.CrossRefPubMedCentralPubMed
23.
Devergne O, Hummel M, Koeppen H, Le Beau MM, Nathanson EC, Kieff E, et al. A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes. J Virol. 1996;70:1143–53.PubMedCentralPubMed
24.
Aparicio-Siegmund S, Moll JM, Lokau J, Grusdat M, Schroder J, Plohn S, et al. Recombinant p35 from bacteria can form interleukin (IL-)12, but not IL-35. PLoS One. 2014;9:e107990.CrossRefPubMedCentralPubMed
25.
Kochetkova I, Golden S, Holderness K, Callis G, Pascual DW. IL-35 stimulation of CD39+ regulatory T cells confers protection against collagen II-induced arthritis via the production of IL-10. J Immunol. 2010;184:7144–53.CrossRefPubMedCentralPubMed
26.
Tirotta E, Duncker P, Oak J, Klaus S, Tsukamoto MR, Gov L, et al. Epstein-Barr virus-induced gene 3 negatively regulates neuroinflammation and T cell activation following coronavirus-induced encephalomyelitis. J Neuroimmunol. 2013;254:110–6.CrossRefPubMed
27.
Huang CH, Loo EX, Kuo IC, Soh GH, Goh DL, Lee BW, et al. Airway inflammation and IgE production induced by dust mite allergen-specific memory/effector Th2 cell line can be effectively attenuated by IL-35. J Immunol. 2011;187:462–7.CrossRefPubMed
28.
Bettini M, Castellaw AH, Lennon GP, Burton AR, Vignali DA. Prevention of autoimmune diabetes by ectopic pancreatic beta-cell expression of interleukin-35. Diabetes. 2012;61:1519–26.CrossRefPubMedCentralPubMed
29.
Niedobitek G, Päzolt D, Teichmann M, Devergne O. Frequent expression of the Epstein-Barr virus (EBV)-induced gene, EBI3, an IL-12 p40-related cytokine, in Hodgkin and reed-Sternberg cells. J Pathol. 2002;198:310–6.CrossRefPubMed
30.
Liyanage UK, Moore TT, Joo HG, Tanaka Y, Herrmann V, Doherty G, et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol. 2002;169:2756–61.CrossRefPubMed
31.
Nishino R, Takano A, Oshita H, Ishikawa N, Akiyama H, Ito H, et al. Identification of Epstein-Barr virus-induced gene 3 as a novel serum and tissue biomarker and a therapeutic target for lung cancer. Clin Cancer Res. 2011;17:6272–86.CrossRefPubMed
32.
Wang Z, Liu JQ, Liu Z, Shen R, Zhang G, Xu J, et al. Tumor-derived IL-35 promotes tumor growth by enhancing myeloid cell accumulation and angiogenesis. J Immunol. 2013;190:2415–23.CrossRefPubMedCentralPubMed
33.
Bardel E, Larousserie F, Charlot-Rabiega P, Coulomb-L'Herminé A, Devergne O. Human CD4+ CD25+ Foxp3+ regulatory T cells do not constitutively express IL-35. J Immunol. 2008;181:6898–05.CrossRefPubMed
34.
Seyerl M, Kirchberger S, Majdic O, Seipelt J, Jindra C, Schrauf C, et al. Human rhinoviruses induce IL-35-producing Treg via induction of B7-H1 (CD274) and sialoadhesin (CD169) on DC. Eur J Immunol. 2010;40:321–9.CrossRefPubMed
35.
Olson BM, Jankowska-Gan E, Becker JT, Vignali DA, Burlingham WJ, McNeel DG. Human prostate tumor antigen-specific CD8+ regulatory T cells are inhibited by CTLA-4 or IL-35 blockade. J Immunol. 2012;189:5590–01.CrossRefPubMedCentralPubMed
36.
Wu H, Li P, Shao N, Ma J, Ji M, Sun X, et al. Aberrant expression of Treg-associated cytokine IL-35 along with IL-10 and TGF-beta in acute myeloid leukemia. Oncol Lett. 2012;3:1119–23.PubMedCentralPubMed
37.
Zeng JC, Zhang Z, Li TY, Liang YF, Wang HM, Bao JJ, et al. Assessing the role of IL-35 in colorectal cancer progression and prognosis. Int J Clin Exp Pathol. 2013;6:1806–16.PubMedCentralPubMed
38.
Jin P, Ren H, Sun W, Xin W, Zhang H, Hao J. CirculatingIL-35 in pancreatic ductal adenocarcinoma patients. Hum Immunol. 2014;75:29–33.CrossRefPubMed
39.
Lin Y, Huang Y, Lu Z, Luo C, Shi Y, Zeng Q, et al. Decreased plasma IL-35 levels are related to the left ventricular ejection fraction in coronary artery diseases. PLoS One. 2012;7:e52490.CrossRefPubMedCentralPubMed
40.
Mao H, Gao W, Ma C, Sun J, Liu J, Shao Q, et al. Human placental trophoblasts express the immunosuppressive cytokine IL-35. Hum Immunol. 2013;74:872–7.CrossRefPubMed
41.
Chen C, Deng Y, Chen H, Wu X, Cheng S, Xu Y, et al. Decreased concentration of IL-35 in plasma of patients with asthma and COPD. Asian Pac J Allergy Immunol. 2014;32:211–7.PubMed
42.
Cooper AM, Kipnis A, Turner J, Magram J, Ferrante J, Orme IM. Mice lacking bioactive IL-12 can generate protective, antigen-specific cellular responses to mycobacterial infection only if the IL-12 p40 subunit is present. J Immunol. 2002;168:1322–7.CrossRefPubMed
43.
Conti HR, Shen F, Nayyar N, Stocum E, Sun JN, Lindemann MJ, et al. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J Exp Med. 2009;206:299–11.CrossRefPubMedCentralPubMed
44.
Shi YY, Dai MJ, Wu GP, Zhou PP, Fang Y, Yan XB. Levels of interleukin-35 and its relationship with regulatory T-cells in chronic hepatitis B patients. Viral Immunol. 2015;28:93–100.CrossRefPubMedCentralPubMed
Metadata
Title
Interleukin-35 on B cell and T cell induction and regulation
Authors
Ai Huang
Lin Cheng
Miao He
Jun Nie
Jianjun Wang
Ke Jiang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Inflammation / Issue 1/2017
Electronic ISSN: 1476-9255
DOI
https://doi.org/10.1186/s12950-017-0164-5

Other articles of this Issue 1/2017

Journal of Inflammation 1/2017 Go to the issue

Commentary

Inflammatory Wnt5A signalling pathways affecting barrier function of human vascular endothelial cells

Research

Successful reduction of inflammatory responses and arachidonic acid–cyclooxygenase 2 pathway in human pulmonary artery endothelial cells by silencing adipocyte fatty acid-binding protein

Review

Neutrophil extracellular traps and the dysfunctional innate immune response of cystic fibrosis lung disease: a review

Research

Ezetimibe reduces cholesterol content and NF-kappaB activation in liver but not in intestinal tissue in guinea pigs

Research

Treatment with 24 h–delayed normo- and hyperbaric oxygenation in severe sepsis induced by cecal ligation and puncture in rats

Research

Hyperoside attenuates dextran sulfate sodium-induced colitis in mice possibly via activation of the Nrf2 signalling pathway
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits