全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
PLOS ONE  2012 

Helminth Antigens Enable CpG-Activated Dendritic Cells to Inhibit the Symptoms of Collagen-induced Arthritis through Foxp3+ Regulatory T Cells

DOI: 10.1371/journal.pone.0040356

Full-Text   Cite this paper   Add to My Lib

Abstract:

Dendritic cells (DC) have the potential to control the outcome of autoimmunity by modulating the immune response. In this study, we tested the ability of Fasciola hepatica total extract (TE) to induce tolerogenic properties in CpG-ODN (CpG) maturated DC, to then evaluate the therapeutic potential of these cells to diminish the inflammatory response in collagen induced arthritis (CIA). DBA/1J mice were injected with TE plus CpG treated DC (T/C-DC) pulsed with bovine collagen II (CII) between two immunizations with CII and clinical scores CIA were determined. The levels of CII-specific IgG2 and IgG1 in sera, the histological analyses in the joints, the cytokine profile in the draining lymph node (DLN) cells and in the joints, and the number, and functionality of CD4+CD25+Foxp3+ T cells (Treg) were evaluated. Vaccination of mice with CII pulsed T/C-DC diminished the severity and incidence of CIA symptoms and the production of the inflammatory cytokine, while induced the production of anti-inflammatory cytokines. The therapeutic effect was mediated by Treg cells, since the adoptive transfer of CD4+CD25+ T cells, inhibited the inflammatory symptoms in CIA. The in vitro blockage of TGF-β in cultures of DLN cells plus CII pulsed T/C-DC inhibited the expansion of Treg cells. Vaccination with CII pulsed T/C-DC seems to be a very efficient approach to diminish exacerbated immune response in CIA, by inducing the development of Treg cells, and it is therefore an interesting candidate for a cell-based therapy for rheumatoid arthritis (RA).

References

[1]  Lubberts E (2008) IL-17/Th17 targeting: on the road to prevent chronic destructive arthritis? Cytokine 41: 84–91.
[2]  Firestein GS (2003) Evolving concepts of rheumatoid arthritis. Nature 423: 356–361.
[3]  Breedveld FC, Combe B (2011) Understanding emerging treatment paradigms in rheumatoid arthritis. Arthritis Res Ther 13: S3.
[4]  Khan S, Greenberg JD, Bhardwaj N (2009) Dendritic cells as targets for therapy in rheumatoid arthritis. Nat Rev Rheumatol 5: 566–571.
[5]  Morelli AE, Thomson AW (2007) Tolerogenic dendritic cells and the quest for transplant tolerance. Nat Rev Immunol 7: 610–621.
[6]  Thomson AW, Robbins PD (2008) Tolerogenic dendritic cells for autoimmune disease and transplantation. Ann Rheum Dis 67: iii90–96.
[7]  van Riet E, Hartgers FC, Yazdanbakhsh M (2007) Chronic helminth infections induce immunomodulation: consequences and mechanisms. Immunobiology 212: 475–490.
[8]  Maizels R (2007) Regulation of the immune system in metazoan parasite infections. Novartis Found Symp 281: 192–204; discussion 204–199.
[9]  Segura M, Su Z, Piccirillo C, Stevenson MM (2007) Impairment of dendritic cell function by excretory-secretory products: a potential mechanism for nematode-induced immunosuppression. Eur J Immunol 37: 1887–1904.
[10]  Hamilton CM, Dowling DJ, Loscher CE, Morphew RM, Brophy PM, et al. (2009) The Fasciola hepatica tegumental antigen suppresses dendritic cell maturation and function. Infect Immun 77: 2488–2498.
[11]  Walsh KP, Brady MT, Finlay CM, Boon L, Mills KH (2009) Infection with a helminth parasite attenuates autoimmunity through TGF-beta-mediated suppression of Th17 and Th1 responses. J Immunol 183: 1577–1586.
[12]  Falcon C, Carranza F, Martinez FF, Knubel CP, Masih DT, et al. (2010) Excretory-secretory products (ESP) from Fasciola hepatica induce tolerogenic properties in myeloid dendritic cells. Vet Immunol Immunopathol 137: 36–46.
[13]  Falcon CR, Carranza FA, Aoki P, Motran CC, Cervi L Adoptive Transfer of Dendritic Cells Pulsed With (2012) Fasciola hepatica Antigens and Lipopolysaccharides Confers Protection Against Fasciolosis in Mice. J Infect Dis. 205: 506–514.
[14]  Cervi L, Rubinstein H, Masih DT (1996) Involvement of excretion-secretion products from Fasciola hepatica inducing suppression of the cellular immune responses. Vet Parasitol 61: 97–111.
[15]  Bianco ID, Balsinde J, Beltramo DM, Castagna LF, Landa CA, et al. (2000) Chitosan-induced phospholipase A2 activation and arachidonic acid mobilization in P388D1 macrophages. FEBS Lett 466: 292–294.
[16]  MacDonald AS, Straw AD, Bauman B, Pearce EJ (2001) CD8- dendritic cell activation status plays an integral role in influencing Th2 response development. J Immunol 167: 1982–1988.
[17]  Kudo Y, Boyd CA (2000) Human placental indoleamine 2,3-dioxygenase: cellular localization and characterization of an enzyme preventing fetal rejection. Biochim Biophys Acta 1500: 119–124.
[18]  Popov I, Li M, Zheng X, San H, Zhang X, et al. (2006) Preventing autoimmune arthritis using antigen-specific immature dendritic cells: a novel tolerogenic vaccine. Arthritis Res Ther 8: R141.
[19]  Campbell IK, Kinkel SA, Drake SF, van Nieuwenhuijze A, Hubert FX, et al. (2009) Autoimmune regulator controls T cell help for pathogenetic autoantibody production in collagen-induced arthritis. Arthritis Rheum 60: 1683–1693.
[20]  Seki N, Sudo Y, Yoshioka T, Sugihara S, Fujitsu T, et al. (1988) Type II collagen-induced murine arthritis. I. Induction and perpetuation of arthritis require synergy between humoral and cell-mediated immunity. J Immunol 140: 1477–1484.
[21]  Gonzalez MA, Gonzalez-Rey E, Rico L, Buscher D, Delgado M (2009) Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cells. Arthritis Rheum 60: 1006–1019.
[22]  Horwitz DA, Zheng SG, Gray JD (2008) Natural and TGF-beta-induced Foxp3(+)CD4(+) CD25(+) regulatory T cells are not mirror images of each other. Trends Immunol 29: 429–435.
[23]  Puccetti P, Grohmann U (2007) IDO and regulatory T cells: a role for reverse signalling and non-canonical NF-kappaB activation. Nat Rev Immunol 7: 817–823.
[24]  Setiady YY, Coccia JA, Park PU (2010) In vivo depletion of CD4+FOXP3+ Treg cells by the PC61 anti-CD25 monoclonal antibody is mediated by FcgammaRIII+ phagocytes. Eur J Immunol 40: 780–786.
[25]  Frick JS, Grunebach F, Autenrieth IB (2010) Immunomodulation by semi-mature dendritic cells: a novel role of Toll-like receptors and interleukin-6. Int J Med Microbiol 300: 19–24.
[26]  Stoop JN, Robinson JH, Hilkens CM (2011) Developing tolerogenic dendritic cell therapy for rheumatoid arthritis: what can we learn from mouse models? Ann Rheum Dis 70: 1526–1533.
[27]  Sidhu M, Griffiths MM, Bradley DS (2009) Vaccination with collagen-pulsed dendritic cells prevents the onset and reduces the disease severity in the mouse model of spontaneous polychondritis. Clin Exp Immunol 157: 350–358.
[28]  van Duivenvoorde LM, Louis-Plence P, Apparailly F, van der Voort EI, Huizinga TW, et al. (2004) Antigen-specific immunomodulation of collagen-induced arthritis with tumor necrosis factor-stimulated dendritic cells. Arthritis Rheum 50: 3354–3364.
[29]  Adorini L, Giarratana N, Penna G (2004) Pharmacological induction of tolerogenic dendritic cells and regulatory T cells. Semin Immunol 16: 127–134.
[30]  van Duivenvoorde LM, Han WG, Bakker AM, Louis-Plence P, Charbonnier LM, et al. (2007) Immunomodulatory dendritic cells inhibit Th1 responses and arthritis via different mechanisms. J Immunol 179: 1506–1515.
[31]  Curotto de Lafaille MA, Lafaille JJ (2009) Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor? Immunity 30: 626–635.
[32]  Chen W, Jin W, Hardegen N, Lei KJ, Li L, et al. (2003) 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.
[33]  Fallarino F, Grohmann U (2011) Using an ancient tool for igniting and propagating immune tolerance: IDO as an inducer and amplifier of regulatory T cell functions. Curr Med Chem 18: 2215–2221.
[34]  Park MJ, Min SY, Park KS, Cho YG, Cho ML, et al. (2008) Indoleamine 2,3-dioxygenase-expressing dendritic cells are involved in the generation of CD4+CD25+ regulatory T cells in Peyer’s patches in an orally tolerized, collagen-induced arthritis mouse model. Arthritis Res Ther 10: R11.
[35]  Pallotta MT, Orabona C, Volpi C, Vacca C, Belladonna ML, et al. (2011) Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells. Nat Immunol 12: 870–878.
[36]  Belladonna ML, Orabona C, Grohmann U, Puccetti P (2009) TGF-beta and kynurenines as the key to infectious tolerance. Trends Mol Med 15: 41–49.
[37]  Sojka DK, Huang YH, Fowell DJ (2008) Mechanisms of regulatory T-cell suppression - a diverse arsenal for a moving target. Immunology 124: 13–22.
[38]  Saraiva M, O’Garra A (2010) The regulation of IL-10 production by immune cells. Nat. Rev. Immunol 10(3): 170–81.
[39]  Gonzalez S, Flo M, Margenat M, Duran R, Gonzalez-Sapienza G, et al. (2009) A family of diverse Kunitz inhibitors from Echinococcus granulosus potentially involved in host-parasite cross-talk. PLoS One 4: e7009.
[40]  Brady MT, O’Neill SM, Dalton JP, Mills KHG (1999) Fasciola hepatica Suppresses a Protective Th1 Response against Bordetella pertussis. Infect Immun 67: 5372–5378.
[41]  Park H, Li Z, Yang XO, Chang SH, Nurieva R, et al. (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6: 1133–1141.
[42]  Nielen MM, van Schaardenburg D, Reesink HW, van de Stadt RJ, van der Horst-Bruinsma IE, et al. (2004) Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum 50: 380–386.
[43]  Harry RA, Anderson AE, Isaacs JD, Hilkens CM (2010) Generation and characterisation of therapeutic tolerogenic dendritic cells for rheumatoid arthritis. Ann Rheum Dis 69: 2042–2050.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133