CoChat
Sign Up
Cited by 309T-cell and B-cell ImmunologyMicroRNA in disease regulationPsoriasis: Treatment and Pathogenesis

MicroRNA-155 Modulates Treg and Th17 Cells Differentiation and Th17 Cell Function by Targeting SOCS1

Open access
Yao, Rui, Ma, Yu-Lan, Liang, Wei, Li, Huan-Huan, Ma, Zhi-Jun, Yu, Xian, Liao, Yu-Hua·2012·PLoS ONE
DOI 10.1371/journal.pone.0046082PMC PMC3473054
Open this paper in CoChat — free accountOpen PDF

Abstract

MicroRNA (miR)-155 is a critical player in both innate and adaptive immune responses. It can influence CD4(+) T cell lineage choice. To clarify the role of miR-155 in CD4(+) CD25(+) regulatory T (Treg)/T helper (Th)17 cell differentiation and function, as well as the mechanism involved, we performed gain-and loss-of-function analysis by transfection pre-miR-155 and anti-miR-155 into purified CD4(+) T cells. The results showed that miR-155 positively regulated both Treg and Th17 cell differentiation. It also induced the release of interleukin (IL)-17A by Th17 cells, but not the release of IL-10 and transforming growth factor (TGF)-β1 by Treg cells. Furthermore, we found that miR-155 reacted through regulating Janus kinase/signal transducer and activator of transcription (JAK/STAT) rather than TGF-β/mothers against decapentaplegic homolog (SMAD) signaling pathway in the process of Treg and Th17 cells differentiation. This may because suppressors of cytokine signaling (SOCS)1, the important negative regulator of JAK/STAT signaling pathway, was the direct target of miR-155 in this process, but SMAD2 and SMAD5 were not. Therefore, we demonstrated that miR-155 enhanced Treg and Th17 cells differentiation and IL-17A production by targeting SOCS1.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0046082

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Increased levels of miR-155 promotes pro-inflammatory cytokine secretion by targeting SOCS1 message for degradation and downregulating anti-inflammatory cytokines that act via JAK/STAT pathway and NF-kB signaling.

    “Increased levels of miR-155 promotes pro-inflammatory cytokine secretion by targeting the Suppressor of Cytokine Signaling 1 (SOCS1) message for degradation and downregulating anti-inflammatory cytokines that act via the JAK/STAT pathway [27, 47] and NF-kB signaling [48].”

    From Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures (2023) · cites this paper as [27]

    The Results report that increased miR-155 lowers SOCS1 protein, increases STAT3/STAT5 phosphorylation, and increases secretion of the pro-inflammatory cytokine IL-17A in activated CD4+ T cells. They do not establish degradation of SOCS1 mRNA, and the Results section on cytokine secretion explicitly reports no significant decrease in the anti-inflammatory cytokines IL-10 or TGF-β1. The NF-κB portion of the citing sentence is attached to a different citation [48]. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • miR-155 targets mRNAs coding for additional molecules involved in suppressing the inflammatory response including SHIP1 and SOCS1, leading to increased pro-inflammatory gene expression.

    “Furthermore, miR-155 targets mRNAs coding for additional molecules involved in suppressing the inflammatory response including, SHIP1 [26] and SOCS1 [27], leading to increased pro-inflammatory gene expression.”

    From Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures (2023) · cites this paper as [27]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 43

  1. [1]Cobb BS, Nesterova TB, Thompson E, Hertweck A, O'Connor E, et al (2005) T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer. J Exp Med 201: 1367– 1373. 15867090 PMC2213187
  2. [2]Muljo SA, Ansel KM, Kanellopoulou C, Livingston DM, Rao A, et al (2005) Aberrant T cell differentiation in the absence of Dicer. J Exp Med 202: 261– 269. 16009718 PMC2212998
  3. [3]Koralov SB, Muljo SA, Galler GR, Krek A, Chakraborty T, et al (2008) Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell 132: 860– 874. 18329371
  4. [4]Chen CZ, Li L, Lodish HF, Bartel DP (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303: 83– 86. 14657504
  5. [6]Nahid MA, Satoh M, Chan EK (2011) Mechanistic role of microRNA-146a in endotoxin-induced differential cross-regulation of TLR signaling. J Immunol 186: 1723– 1734. 21178010 PMC3608687
  6. [7]O'Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D (2007) MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A 104: 1604– 1609. 17242365 PMC1780072
  7. [8]Ruggiero T, Trabucchi M, De Santa F, Zupo S, Harfe BD, et al (2009) LPS induces KH-type splicing regulatory protein-dependent processing of microRNA-155 precursors in macrophages. FASEB J 23: 2898– 2908. 19423639
  8. [9]Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, et al (2007) Regulation of the germinal center response by MicroRNA-155. Science 316: 604– 608. 17463289
  9. [11]Askenasy N, Kaminitz A, Yarkoni S (2008) Mechanisms of T regulatory cell function. Autoimmun Rev 7: 370– 375. 18486924
  10. [12]Bettelli E, Korn T, Oukka M, Kuchroo VK (2008) Induction and effector functions of T(H)17 cells. Nature 453: 1051– 1057. 18563156 PMC6280661
  11. [13]Kohlhaas S, Garden OA, Scudamore C, Turner M, Okkenhaug K, et al (2009) Cutting edge: the Foxp3 target miR-155 contributes to the development of regulatory T cells. J Immunol 182: 2578– 2582. 19234151
  12. [14]Lu LF, Thai TH, Calado DP, Chaudhry A, Kubo M, et al (2009) Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity 30: 80– 91. 19144316 PMC2654249
  13. [15]O'Connell RM, Kahn D, Gibson WS, Round JL, Scholz RL, et al (2010) MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity 33: 607– 619. 20888269 PMC2966521
  14. [16]Numata K, Kubo M, Watanabe H, Takagi K, Mizuta H, et al (2007) Overexpression of suppressor of cytokine signaling-3 in T cells exacerbates acetaminophen-induced hepatotoxicity. J Immunol 178: 3777– 3785. 17339476
  15. [17]Zhan Y, Davey GM, Graham KL, Kiu H, Dudek NL, et al (2009) SOCS1 negatively regulates the production of Foxp3+ CD4+ T cells in the thymus. Immunol Cell Biol 87: 473– 480. 19381159
  16. [18]Flowers LO, Subramaniam PS, Johnson HM (2005) A SOCS-1 peptide mimetic inhibits both constitutive and IL-6 induced activation of STAT3 in prostate cancer cells. Oncogene 24: 2114– 2120. 15688010
  17. [19]Jager LD, Dabelic R, Waiboci LW, Lau K, Haider MS, et al (2011) The kinase inhibitory region of SOCS-1 is sufficient to inhibit T-helper 17 and other immune functions in experimental allergic encephalomyelitis. J Neuroimmunol 232: 108– 118. 21131060 PMC3053067
  18. [20]Yu CR, Mahdi RR, Oh HM, Amadi-Obi A, Levy-Clarke G, et al (2011) Suppressor of cytokine signaling-1 (SOCS1) inhibits lymphocyte recruitment into the retina and protects SOCS1 transgenic rats and mice from ocular inflammation. Invest Ophthalmol Vis Sci 52: 6978– 6986. 21778271 PMC3176005
  19. [21]Mujtaba MG, Flowers LO, Patel CB, Patel RA, Haider MI, et al (2005) Treatment of mice with the suppressor of cytokine signaling-1 mimetic peptide, tyrosine kinase inhibitor peptide, prevents development of the acute form of experimental allergic encephalomyelitis and induces stable remission in the chronic relapsing/remitting form. J Immunol 175: 5077– 5086. 16210611
  20. [22]Wei L, Laurence A, O'Shea JJ (2008) New insights into the roles of Stat5a/b and Stat3 in T cell development and differentiation. Semin Cell Dev Biol 19: 394– 400. 18708155 PMC2657870
  21. [23]Liu X, Lee YS, Yu CR, Egwuagu CE (2008) Loss of STAT3 in CD4+ T cells prevents development of experimental autoimmune diseases. J Immunol 180: 6070– 6076. 18424728 PMC2435016
  22. [24]Turka LA, Walsh PT (2008) IL-2 signaling and CD4+ CD25+ Foxp3+ regulatory T cells. Front Biosci 13: 1440– 1446. 17981641
  23. [25]Fontenot JD, Rasmussen JP, Gavin MA, Rudensky AY (2005) A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol 6: 1142– 1151. 16227984
  24. [26]Weniger MA, Melzner I, Menz CK, Wegener S, Bucur AJ, et al (2006) Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation. Oncogene 25: 2679– 2684. 16532038
  25. [27]Lee TL, Yeh J, Van Waes C, Chen Z (2006) Epigenetic modification of SOCS-1 differentially regulates STAT3 activation in response to interleukin-6 receptor and epidermal growth factor receptor signaling through JAK and/or MEK in head and neck squamous cell carcinomas. Mol Cancer Ther 5: 8– 19. 16432158
  26. [28]Chen W, Jin W, Hardegen N, Lei KJ, Li L, et al (2002) Conversion of peripheral CD4+CD25− naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198: 1875– 1886. PMC2194145 14676299
  27. [30]Louafi F, Martinez-Nunez RT, Sanchez-Elsner T (2010) MicroRNA-155 targets SMAD2 and modulates the response of macrophages to transforming growth factor-{beta}. J Biol Chem 285: 41328– 41336. 21036908 PMC3009858
  28. [31]Rai D, Kim SW, McKeller MR, Dahia PL, Aguiar RC (2010) Targeting of SMAD5 links microRNA-155 to the TGF-beta pathway and lymphomagenesis. Proc Natl Acad Sci U S A 107: 3111– 3116. 20133617 PMC2840369
  29. [32]Murugaiyan G, Beynon V, Mittal A, Joller N, Weiner HL (2011) Silencing microRNA-155 ameliorates experimental autoimmune encephalomyelitis. J Immunol 187: 2213– 2221. 21788439 PMC3167080
  30. [33]Durant L, Watford WT, Ramos HL, Laurence A, Vahedi G, et al (2010) Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity 32: 605– 615. 20493732 PMC3148263
  31. [34]Kimura A, Kishimoto T (2010) IL-6: regulator of Treg/Th17 balance. Eur J Immunol 40: 1830– 1835. 20583029
  32. [35]Mills KH (2008) Induction, function and regulation of IL-17-producing T cells. Eur J Immunol 38: 2636– 2649. 18958872
  33. [36]Adamson AS, Collins K, Laurence A, O'Shea JJ (2009) The Current STATus of lymphocyte signaling: new roles for old players. Curr Opin Immunol 21: 161– 166. 19362457 PMC2692054
  34. [37]Wang P, Hou J, Lin L, Wang C, Liu X, et al (2010) Inducible microRNA-155 feedback promotes type I IFN signaling in antiviral innate immunity by targeting suppressor of cytokine signaling 1. J Immunol 185: 6226– 6233. 20937844
  35. [38]Lu C, Huang X, Zhang X, Roensch K, Cao Q, et al (2011) MiR-221 and miR-155 regulate human dendritic cell development, apoptosis, and IL-12 production through targeting of p27kip1, KPC1, and SOCS-1. Blood 117: 4293– 4303. 21355095 PMC3087479
  36. [39]Isomäki P, Alanärä T, Isohanni P, Lagerstedt A, Korpela M, et al (2007) The expression of SOCS is altered in rheumatoid arthritis. Rheumatology (Oxford) 46: 1538– 1546. 17726036
  37. [40]Chan HC, Ke LY, Chang LL, Liu CC, Hung YH, et al (2010) Suppressor of cytokine signaling 1 gene expression and polymorphisms in systemic lupus erythematosus. Lupus 19: 696– 702. 20064913
  38. [41]Gómez-Guerrero C, López-Franco O, Sanjuán G, Hernández-Vargas P, Suzuki Y, et al (2004) Suppressors of cytokine signaling regulate Fc receptor signaling and cell activation during immune renal injury. J Immunol 172: 6969– 6977. 15153517
  39. [42]Ortiz-Muñoz G, Martin-Ventura JL, Hernandez-Vargas P, Mallavia B, Lopez-Parra V, et al (2009) Suppressors of cytokine signaling modulate JAK/STAT-mediated cell responses during atherosclerosis. Arterioscler Thromb Vasc Biol 29: 525– 531. 19164812
  40. [43]McLaren JE, Ramji DP (2009) Interferon gamma: a master regulator of atherosclerosis. Cytokine. Growth Factor Rev 20: 125– 135. 19041276
  41. [44]Faraoni I, Antonetti FR, Cardone J, Bonmassar E (2009) MiR-155 gene: a typical multifunctional microRNA. Biochim Biophys Acta 1792: 497– 505. 19268705
  42. [45]Xie JJ, Wang J, Tang TT, Chen J, Gao XL, et al (2010) The Th17/Treg functional imbalance during atherogenesis in ApoE(−/−) mice. Cytokine 49: 185– 193. 19836260
  43. [46]Yu HR, Chang JC, Chen RF, Chuang H, Hong KC, et al (2003) Different antigens trigger different Th1/Th2 reactions in neonatal mononuclear cells (MNCs) relating to T-bet/GATA-3 expression. J Leukoc Biol 74: 952– 958. 12960249

Cited by

Sorted by citations

Authors
Yao, R., Ma, Y.-L., Liang, W., Li, H.-H., Ma, Z.-J., Yu, X., & Liao, Y.-H.
Affiliations
Wuhan Union Hospital (CN)
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-10-16
Volume
7
Issue
10
Pages
e46082
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0046082
PMC
PMC3473054
OpenAlex
W2007711648
Cited by
309
References
3
Citations by year
2026: 14 · 2025: 18 · 2024: 16 · 2023: 17 · 2022: 26 · 2021: 25 · 2020: 32 · 2019: 27 · 2018: 22 · 2017: 24 · 2016: 27 · 2015: 16 · 2014: 27 · 2013: 17 · 2012: 1
FWCI
8.53
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81000085)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords
miR-155, SOCS1, regulatory T cells, Th17 cells, CD4+ T cell differentiation, IL-17A, JAK/STAT signaling, Smad2, Smad5, TGF-beta signaling
MeSH terms
Suppressor of Cytokine Signaling 1 Protein, T-bet Transcription Factor, Animals, Base Sequence, Cell Differentiation, Gene Expression Regulation, Interferon-gamma, Signal Transduction, Interleukin-4, Interleukin-10, Interleukin-17, T-Box Domain Proteins, MicroRNAs, T-Lymphocytes, Regulatory, STAT Transcription Factors, Suppressor of Cytokine Signaling Proteins, GATA3 Transcription Factor, Mice, Smad Proteins, Forkhead Transcription Factors, Janus Kinases, Transforming Growth Factor beta1, Nuclear Receptor Subfamily 1, Group F, Member 3, Th17 Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review