nach oben

Immunologic Research

Erschienen in:

11.05.2018 | Review

IL-35: a new immunomodulator in autoimmune rheumatic diseases

verfasst von: Lazaros I. Sakkas, Athanasios Mavropoulos, Carlo Perricone, Dimitrios P. Bogdanos

Erschienen in: Immunologic Research | Ausgabe 3/2018

Einloggen, um Zugang zu erhalten

Abstract

IL-35 is a relatively new cytokine that emerges as an important immunomodulator. IL-35 belongs to IL-12 cytokine family that includes IL-12, IL-23, IL-27, and IL-35. These cytokines are heterodimers that share subunits and their receptors also share subunits. Whereas IL-12 and IL-23 are clearly proinflammatory cytokines, the role of IL-35 is less clear. In mice, IL-35 appears to be anti-inflammatory and to protect from autoimmune inflammatory diseases. IL-35 induces the expansion of a subset of regulatory T cells (Tregs) and Bregs and mediates their suppressive function and inhibits Th17 cells. It also upregulates osteoprotegerin and suppresses RANKL, thus inhibiting bone resorption. In autoimmune rheumatic diseases, findings are conflicting, although in systemic lupus erythematosus, there is reduced function of IL-35. In psoriatic arthritis, a disease characterized by bone erosion and bone formation in peripheral joints and bone formation in spinal joints, serum levels of IL-35 were found increased in one study. Further data are required to define the exact role of IL-35 in human autoimmune rheumatic diseases.

Pope RM, Shahrara S. Possible roles of IL-12-family cytokines in rheumatoid arthritis. Nat Rev Rheumatol. 2013;9(4):252–6. https://doi.org/10.1038/nrrheum.2012.170.CrossRefPubMed

Sun L, He C, Nair L, Yeung J, Egwuagu CE. Interleukin 12 (IL-12) family cytokines: Role in immune pathogenesis and treatment of CNS autoimmune disease. Cytokine. 2015;75(2):249–55. https://doi.org/10.1016/j.cyto.2015.01.030.CrossRefPubMedPubMedCentral

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(22):12041–6.CrossRefPubMedPubMedCentral

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(7169):566–9. https://doi.org/10.1038/nature06306.CrossRefPubMed

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(6):633–41. https://doi.org/10.1038/nm.3554.CrossRefPubMedPubMedCentral

Li X, Mai J, Virtue A, Yin Y, Gong R, Sha X, et al. IL-35 is a novel responsive anti-inflammatory cytokine--a new system of categorizing anti-inflammatory cytokines. PLoS One. 2012;7(3):e33628. https://doi.org/10.1371/journal.pone.0033628/PONE-D-11-22823.CrossRefPubMedPubMedCentral

Bardel E, Larousserie F, Charlot-Rabiega P, Coulomb-L’Hermine A, Devergne O. Human CD4 + CD25 + Foxp3 + regulatory T cells do not constitutively express IL-35. J Immunol. 2008;181(10):6898–905.CrossRefPubMed

Wei X, Zhang J, Gu Q, Huang M, Zhang W, Guo J, et al. Reciprocal Expression of IL-35 and IL-10 Defines Two Distinct Effector Treg Subsets that Are Required for Maintenance of Immune Tolerance. Cell Rep. 2017;21(7):1853–69. https://doi.org/10.1016/j.celrep.2017.10.090.CrossRefPubMed

Tedder TF, Leonard WJ. Autoimmunity: regulatory B cells--IL-35 and IL-21 regulate the regulators. Nat Rev Rheumatol. 2014;10(8):452–3. https://doi.org/10.1038/nrrheum.2014.95.CrossRefPubMed

10.

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(7492):366–70. https://doi.org/10.1038/nature12979.CrossRefPubMedPubMedCentral

11.

Dambuza IM, He C, Choi JK, Yu CR, Wang R, Mattapallil MJ, et al. IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease. Nat Commun. 2017;8(1):719. https://doi.org/10.1038/s41467-017-00838-4.CrossRefPubMedPubMedCentral

12.

Haller S, Duval A, Migliorini R, Stevanin M, Mack V, Acha-Orbea H. Interleukin-35-Producing CD8alpha(+) Dendritic Cells Acquire a Tolerogenic State and Regulate T Cell Function. Front Immunol. 2017;8:98. https://doi.org/10.3389/fimmu.2017.00098.CrossRefPubMedPubMedCentral

13.

Meka RR, Venkatesha SH, Dudics S, Acharya B, Moudgil KD. IL-27-induced modulation of autoimmunity and its therapeutic potential. Autoimmun Rev. 2015;14(12):1131–41. https://doi.org/10.1016/j.autrev.2015.08.001.CrossRefPubMedPubMedCentral

14.

Neurath MF. IL-12 family members in experimental colitis. Mucosal Immunol. 2008;1(Suppl 1):S28–30. https://doi.org/10.1038/mi.2008.45.CrossRefPubMed

15.

Choi JK, Dambuza IM, He C, Yu CR, Uche AN, Mattapallil MJ, et al. IL-12p35 Inhibits Neuroinflammation and Ameliorates Autoimmune Encephalomyelitis. Front Immunol. 2017;8:1258. https://doi.org/10.3389/fimmu.2017.01258.CrossRefPubMedPubMedCentral

16.

Cho KA, Lee JK, Kim YH, Park M, Woo SY, Ryu KH. Mesenchymal stem cells ameliorate B-cell-mediated immune responses and increase IL-10-expressing regulatory B cells in an EBI3-dependent manner. Cell Mol Immunol. 2017; https://doi.org/10.1038/cmi.2016.59.

17.

Chehboun S, Labrecque-Carbonneau J, Pasquin S, Meliani Y, Meddah B, Ferlin W, et al. Epstein-Barr virus-induced gene 3 (EBI3) can mediate IL-6 trans-signaling. J Biol Chem. 2017;292(16):6644–56. https://doi.org/10.1074/jbc.M116.762021.CrossRefPubMedPubMedCentral

18.

Sonmez C, Yucel AA, Yesil TH, Kucuk H, Sezgin B, Mercan R, et al. Correlation between IL-17A/F, IL-23, IL-35 and IL-12/-23 (p40) levels in peripheral blood lymphocyte cultures and disease activity in Behcet's patients. Clin Rheumatol. 2018; https://doi.org/10.1007/s10067-018-4049-7.

19.

He D, Liu M, Liu B. Interleukin-35 as a New Biomarker of Renal Involvement in Lupus Nephritis Patients. Tohoku J Exp Med. 2018;244(4):263–70. https://doi.org/10.1620/tjem.244.263.CrossRefPubMed

20.

Ouyang H, Shi YB, Liu ZC, Wang Z, Feng S, Kong SM, et al. Decreased interleukin 35 and CD4 + EBI3 + T cells in patients with active systemic lupus erythematosus. Am J Med Sci. 2014;348(2):156–61. https://doi.org/10.1097/MAJ.000000000000021500000441-201408000-00012.CrossRefPubMed

21.

Cai Z, Wong CK, Kam NW, Dong J, Jiao D, Chu M, et al. Aberrant expression of regulatory cytokine IL-35 in patients with systemic lupus erythematosus. Lupus. 2015;24(12):1257–66. https://doi.org/10.1177/0961203315585815.CrossRefPubMed

22.

Cai Z, Wong CK, Dong J, Chu M, Jiao D, Kam NW, et al. Remission of systemic lupus erythematosus disease activity with regulatory cytokine interleukin (IL)-35 in Murphy Roths Large (MRL)/lpr mice. Clin Exp Immunol. 2015;181(2):253–66. https://doi.org/10.1111/cei.12639.CrossRefPubMedPubMedCentral

23.

Zhang Y, Li J, Zhou N, Zhang Y, Wu M, Xu J, et al. The unknown aspect of BAFF: inducing IL-35 production by a CD5(+)CD1d(hi)FcgammaRIIb(hi) regulatory B-cell subset in lupus. J Invest Dermatol. 2017;137(12):2532–43. https://doi.org/10.1016/j.jid.2017.07.843.CrossRefPubMed

24.

Nakano S, Morimoto S, Suzuki S, Tsushima H, Yamanaka K, Sekigawa I, et al. Immunoregulatory role of IL-35 in T cells of patients with rheumatoid arthritis. Rheumatology (Oxford). 2015;54(8):1498–506. https://doi.org/10.1093/rheumatology/keu528.CrossRef

25.

Ning X, Jian Z, Wang W. Low Serum Levels of Interleukin 35 in Patients with Rheumatoid Arthritis. Tohoku J Exp Med. 2015;237(2):77–82. https://doi.org/10.1620/tjem.237.77.CrossRefPubMed

26.

Yin L, Ge Y, Yang H, Peng Q, Lu X, Zhang Y, et al. The clinical utility of serum IL-35 in patients with polymyositis and dermatomyositis. Clin Rheumatol. 2016;35(11):2715–21. https://doi.org/10.1007/s10067-016-3347-1.CrossRefPubMed

27.

Senolt L, Sumova B, Jandova R, Hulejova H, Mann H, Pavelka K, et al. Interleukin 35 Synovial Fluid Levels Are Associated with Disease Activity of Rheumatoid Arthritis. PLoS One. 2015;10(7):e0132674. https://doi.org/10.1371/journal.pone.0132674PONE-D-15-13352.CrossRefPubMedPubMedCentral

28.

Filkova M, Vernerova Z, Hulejova H, Prajzlerova K, Veigl D, Pavelka K, et al. Pro-inflammatory effects of interleukin-35 in rheumatoid arthritis. Cytokine. 2015;73(1):36–43. https://doi.org/10.1016/j.cyto.2015.01.019.CrossRefPubMed

29.

Kam NW, Liu D, Cai Z, Mak WY, Wong CK, Chiu KH, et al. Synoviocytes-derived Interleukin 35 Potentiates B Cell Response in Patients with Osteoarthritis and Rheumatoid Arthritis. J Rheumatol. 2017; https://doi.org/10.3899/jrheum.161363.

30.

Kudo H, Wang Z, Jinnin M, Nakayama W, Inoue K, Honda N, et al. EBI3 Downregulation Contributes to Type I Collagen Overexpression in Scleroderma Skin. J Immunol. 2015;195(8):3565–73. https://doi.org/10.4049/jimmunol.1402362.CrossRefPubMed

31.

Tomcik M, Zerr P, Palumbo-Zerr K, Storkanova H, Hulejova H, Spiritovic M, et al. Interleukin-35 is upregulated in systemic sclerosis and its serum levels are associated with early disease. Rheumatology (Oxford). 2015;54(12):2273–82. https://doi.org/10.1093/rheumatology/kev260.CrossRef

32.

Dantas AT, Goncalves SM, Pereira MC, Goncalves RS, Marques CD, Rego MJ, et al. Increased IL-35 serum levels in systemic sclerosis and association with pulmonary interstitial involvement. Clin Rheumatol. 2015;34(9):1621–5. https://doi.org/10.1007/s10067-015-3006-y.CrossRefPubMed

33.

Fogel O, Riviere E, Seror R, Nocturne G, Boudaoud S, Ly B, et al. Role of the IL-12/IL-35 balance in patients with Sjogren syndrome. J Allergy Clin Immunol. 2017; https://doi.org/10.1016/j.jaci.2017.07.041.

34.

Li J, Liu L, Rui W, Li X, Xuan D, Zheng S, et al. New Interleukins in Psoriasis and Psoriatic Arthritis Patients: The Possible Roles of Interleukin-33 to Interleukin-38 in Disease Activities and Bone Erosions. Dermatology. 2017;233(1):37–46. https://doi.org/10.1159/000471798. CrossRefPubMed

35.

Niedbala W, Wei XQ, Cai B, Hueber AJ, Leung BP, McInnes IB, et al. 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(11):3021–9. https://doi.org/10.1002/eji.200737810.CrossRefPubMed

36.

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(12):7144–53. https://doi.org/10.4049/jimmunol.0902739.CrossRefPubMedPubMedCentral

37.

Li Y, Wu S, Li Y, Jiang S, Lin T, Xia L, et al. Interleukin-35 (IL-35) inhibits proliferation and promotes apoptosis of fibroblast-like synoviocytes isolated from mice with collagen-induced arthritis. Mol Biol Rep. 2016;43(9):947–56. https://doi.org/10.1007/s11033-016-4034-7.CrossRefPubMed

38.

Jiang S, Li Y, Lin T, Yuan L, Li Y, Wu S, et al. IL-35 Inhibits Angiogenesis through VEGF/Ang2/Tie2 Pathway in Rheumatoid Arthritis. Cell Physiol Biochem. 2016;40(5):1105–16. https://doi.org/10.1159/000453165.CrossRefPubMed

39.

Wu S, Li Y, Li Y, Yao L, Lin T, Jiang S, et al. Interleukin-35 attenuates collagen-induced arthritis through suppression of vascular endothelial growth factor and its receptors. Int Immunopharmacol. 2016;34:71–7. https://doi.org/10.1016/j.intimp.2016.02.018.CrossRefPubMed

40.

Dixon KO, van der Kooij SW, Vignali DA, van Kooten C. Human tolerogenic dendritic cells produce IL-35 in the absence of other IL-12 family members. Eur J Immunol. 2015;45(6):1736–47. https://doi.org/10.1002/eji.201445217.CrossRefPubMedPubMedCentral

41.

Li Y, Li D, Li Y, Wu S, Jiang S, Lin T, et al. Interleukin-35 upregulates OPG and inhibits RANKL in mice with collagen-induced arthritis and fibroblast-like synoviocytes. Osteoporos Int. 2016;27(4):1537–46. https://doi.org/10.1007/s00198-015-3410-9.CrossRefPubMed

42.

Thiolat A, Denys A, Petit M, Biton J, Lemeiter D, Herve R, et al. Interleukin-35 gene therapy exacerbates experimental rheumatoid arthritis in mice. Cytokine. 2014;69(1):87–93. https://doi.org/10.1016/j.cyto.2014.05.015.CrossRefPubMed

43.

Gao W, Sweeney C, Walsh C, Rooney P, McCormick J, Veale DJ, et al. Notch signalling pathways mediate synovial angiogenesis in response to vascular endothelial growth factor and angiopoietin 2. Ann Rheum Dis. 2013;72(6):1080–8. https://doi.org/10.1136/annrheumdis-2012-201978.CrossRefPubMed

44.

Sakkas LI, Chikanza IC, Platsoucas CD. Mechanisms of Disease: the role of immune cells in the pathogenesis of systemic sclerosis. Nat Clin Pract Rheumatol. 2006;2(12):679–85. https://doi.org/10.1038/ncprheum0346.CrossRefPubMed

45.

Sakkas LI, Bogdanos DP. Systemic sclerosis: New evidence re-enforces the role of B cells. Autoimmun Rev. 2016;15(2):155–61. https://doi.org/10.1016/j.autrev.2015.10.005.CrossRefPubMed

46.

Mavropoulos A, Simopoulou T, Varna A, Liaskos C, Katsiari C, Bogdanos DP, et al. B regulatory cells are decreased and functionally impaired in patients with systemic sclerosis. Arthritis Rheumatol. 2015; https://doi.org/10.1002/art.39437.

47.

Matsushita T, Hamaguchi Y, Hasegawa M, Takehara K, Fujimoto M. Decreased levels of regulatory B cells in patients with systemic sclerosis: association with autoantibody production and disease activity. Rheumatology (Oxford). 2016;55(2):263–7. https://doi.org/10.1093/rheumatology/kev331.CrossRef

48.

Malik A, Hayat G, Kalia JS, Guzman MA. Idiopathic Inflammatory Myopathies: Clinical Approach and Management. Front Neurol. 2016;7:64. https://doi.org/10.3389/fneur.2016.00064.CrossRefPubMedPubMedCentral

49.

Sakkas LI, Bogdanos DP. Are psoriasis and psoriatic arthritis the same disease? The IL-23/IL-17 axis data. Autoimmun Rev. 2017;16(1):10–5. https://doi.org/10.1016/j.autrev.2016.09.015.CrossRefPubMed

Titel: IL-35: a new immunomodulator in autoimmune rheumatic diseases
verfasst von: Lazaros I. Sakkas
Athanasios Mavropoulos
Carlo Perricone
Dimitrios P. Bogdanos
Publikationsdatum: 11.05.2018
Verlag: Springer US
Erschienen in: Immunologic Research / Ausgabe 3/2018
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI: https://doi.org/10.1007/s12026-018-8998-3

Neu im Fachgebiet HNO

16.04.2024 | HNO-Chirurgie | Nachrichten

Update HNO

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.

Newsletter bestellen

Springer Medizin

IL-35: a new immunomodulator in autoimmune rheumatic diseases

Abstract

Neu im Fachgebiet HNO

HNO-Op. auch mit über 90?

Intrakapsuläre Tonsillektomie gewinnt an Boden

Bilateraler Hörsturz hat eine schlechte Prognose

„Nur wer sich gut aufgehoben fühlt, kann auch für Patientensicherheit sorgen“

Update HNO

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2018

The class D scavenger receptor CD68 contributes to mouse chronic liver injury

Effects of crocin on inflammatory activities in human fibroblast-like synoviocytes and collagen-induced arthritis in mice

Co-appearance of OPV and BCG vaccine-derived complications in two infants with severe combined immunodeficiency

Impact of mast cells in depression disorder: inhibitory effect of IL-37 (new frontiers)

Role of T cell-derived exosomes in immunoregulation

Antibodies to small ubiquitin-like modifier activating enzyme are associated with a diagnosis of dermatomyositis: results from an unselected cohort

Neu im Fachgebiet HNO

HNO-Op. auch mit über 90?

Intrakapsuläre Tonsillektomie gewinnt an Boden

Bilateraler Hörsturz hat eine schlechte Prognose

„Nur wer sich gut aufgehoben fühlt, kann auch für Patientensicherheit sorgen“

Update HNO