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2011 | 11 | 2 | 100-105
Article title

Limfocyty Th17 w patogenezie doświadczalnego modelu stwardnienia rozsianego

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Title variants
EN
Th17 cells in pathogenesis of experimental model of multiple sclerosis
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PL
Abstracts
EN
Th17 cells are quite recently discovered subpopulation of T helper lymphocytes, characterized by the production of IL-17 (IL-17). Research on these lymphocytes gives new light on the pathogenesis of multiple sclerosis (MS) and its experimental model (EAE). These lymphocytes have a high similarity to Th1 cells and naïve T CD4+ differentiate into Th17 phenotype under the influence of a specific set of cytokines. Formation of murine Th17 cells is induced by cytokines TGF-β and IL-6 or IL-21. Th17 cells produce various chemokines, including IL-17A/F, IL-21 and IL-22. It has been documented that the neutralization of IL-17 reduces the symptoms of the disease in an animal model of MS. The main mediator of central nervous system (CNS) pathology induced by Th17 cells is IL-17A. One of the best characterized function of IL-17A is the induction of the production of neutrophilic CXC ELR+ chemokines: CXCL1 and CXCL2. Moreover, Th17 cells can promote the development of EAE by activation of neutrophils within the bone marrow, which in consequences leads to the mobilization of immature monocytes into the bloodstream and the development ofinflammation in the CNS. A growing number of data from the studies on MS and EAE confirms a major role of Th17 lymphocytes in the pathogenesis of this disease. Understanding the exact role of these cells requires further studies, since their results may be useful in developing new therapies for MS.
PL
Limfocyty Th17 są stosunkowo niedawno opisaną subpopulacją limfocytów pomocniczych T (Th), charakteryzującą się wytwarzaniem cytokiny IL-17 (IL-17). Badania nad tymi limfocytami rzuciły nowe światło na patogenezę stwardnienia rozsianego (SM) i jego doświadczalnego modelu – eksperymentalnego autoimmunizacyjnego zapalenia mózgu i rdzenia kręgowego (experimental autoimmune encephalomyelitis, EAE). Limfocyty te wykazują znaczne podobieństwo do limfocytów Th1, a dziewicze limfocyty CD4+ różnicują się w kierunku fenotypu Th17 pod wpływem stymulacji ściśle określonego zestawu cytokin. Powstawanie mysich limfocytów Th17 indukują cytokiny TGF-β oraz IL-6 lub IL-21. Komórki Th17 produkują różne chemokiny, m.in. IL-17A/F, IL-21 i IL-22. Udokumentowano, że neutralizacja IL-17 zmniejsza objawy choroby EAE. Głównym mediatorem stanu patologicznego w ośrodkowym układzie nerwowym (OUN) indukowanego przez limfocyty Th17 jest cytokina IL-17A. Do najlepiej scharakteryzowanych funkcji IL-17A należy indukcja wytwarzania neutrofilowych chemokin ELR+ CXC, tj. CXCL1 i CXCL2. Ponadto limfocyty Th17 mogą sprzyjać rozwojowi EAE poprzez aktywację neutrofili wewnątrz szpiku kostnego, co w konsekwencji prowadzi do mobilizacji niedojrzałych monocytów do krwiobiegu i rozwoju zapalenia w ośrodkowym układzie nerwowym. Rosnąca liczba danych płynących z badań nad SM i EAE potwierdza istotny udział limfocytów Th17 w patogenezie tej choroby, a poznanie dokładnej roli tych limfocytów wymaga dalszych badań – ich wyniki mogą być użyteczne w opracowywaniu nowych metod terapii SM.
Discipline
Publisher

Year
Volume
11
Issue
2
Pages
100-105
Physical description
Contributors
  • Oddział Kliniczny Propedeutyki Neurologicznej z Pododdziałem Udarowym, Uniwersytet Medyczny w Łodzi, WSS. im. M. Kopernika
  • Oddział Kliniczny Propedeutyki Neurologicznej z Pododdziałem Udarowym, Uniwersytet Medyczny w Łodzi, WSS. im. M. Kopernika
References
  • 1. Juszczak M., Głąbiński A.: Udział limfocytów Th17 w patogenezie stwardnienia rozsianego. Postępy Hig. Med. Dośw. 2009; 63: 492-501.
  • 2. Carlson T., Kroenke M., Rao P. i wsp.: The Th17-ELR+ CXC chemokine pathway is essential for the development of central nervous system autoimmune disease. J. Exp. Med. 2008; 205: 811-823.
  • 3. Korn T., Oukka M., Kuchroo V., Bettelli E.: Th17 cells: effector T cells with inflammatory properties. Semin. Immunol. 2007; 19: 362-371.
  • 4. Mosmann T.R., Coffman R.L.: TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. Immunol. 1989; 7: 145-173.
  • 5. Rouvier E., Luciani M.F., Mattéi M.G. i wsp.: CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J. Immunol. 1993; 150: 5445-5456.
  • 6. Kolls J.K., Lindén A.: Interleukin-17 family members and inflammation. Immunity 2004; 21: 467-476.
  • 7. Toy D., Kugler D., Wolfson M. i wsp.: Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J. Immunol. 2006; 177: 36-39.
  • 8. Moseley T.A., Haudenschild D.R., Rose L., Reddi A.H.: Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev. 2003; 14: 155-174.
  • 9. Kramer J.M., Yi L., Shen F. i wsp.: Evidence for ligand-independent multimerization of the IL-17 receptor. J. Immunol. 2006; 176: 711-715.
  • 10. Ferretti S., Bonneau O., Dubois G.R. i wsp.: IL-17, produced by lymphocytes and neutrophils, is necessary for lipopolysaccharide- induced airway neutrophilia: IL-15 as a possible trigger. J. Immunol. 2003; 170: 2106-2112.
  • 11. Lankford C.S., Frucht D.M.: A unique role for IL-23 in promoting cellular immunity. J. Leukoc. Biol. 2003; 73: 49-56.
  • 12. Shi Y., Ullrich S.J., Zhang J. i wsp.: A novel cytokine receptor- ligand pair. Identification, molecular characterization, and in vivo immunomodulatory activity. J. Biol. Chem. 2000; 275: 19167-19176.
  • 13. Starnes T., Broxmeyer H.E., Robertson M.J., Hromas R.: Cutting edge: IL-17D, a novel member of the IL-17 family, stimulates cytokine production and inhibits hemopoiesis. J. Immunol. 2002; 169: 642-646.
  • 14. Lee J., Ho W.H., Maruoka M. i wsp.: IL-17E, a novel proinflammatory ligand for the IL-17 receptor homolog IL-17Rh1. J. Biol. Chem. 2001; 276: 1660-1664.
  • 15. Ikeda K., Nakajima H., Suzuki K. i wsp.: Mast cells produce interleukin-25 upon FcεRI-mediated activation. Blood 2003; 101: 3594-3596.
  • 16. Bettelli E., Carrier Y., Gao W. i wsp.: Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006; 441: 235-238.
  • 17. Korn T., Bettelli E., Gao W. i wsp.: IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells. Nature 2007; 448: 484-487.
  • 18. Zhou L., Lopes J.E., Chong M.M. i wsp.: TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function. Nature 2008; 453: 236-240.
  • 19. McGeachy M.J., Bak-Jensen K.S., Chen Y. i wsp.: TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell-mediated pathology. Nat. Immunol. 2007; 8: 1390-1397.
  • 20. Nakae S., Iwakura Y., Suto H., Galli S.J.: Phenotypic differences between Th1 and Th17 cells and negative regulation of Th1 cell differentiation by IL-17. J. Leukoc. Biol. 2007; 81: 1258-1268.
  • 21. Mangelsdorf D.J., Evans R.M.: The RXR heterodimers and orphan receptors. Cell 1995; 83: 841-850.
  • 22. Eberl G., Littman D.R.: The role of the nuclear hormone receptor RORγt in the development of lymph nodes and Peyer’s patches. Immunol. Rev. 2003; 195: 81-90.
  • 23. Sun Z., Unutmaz D., Zou Y.R. i wsp.: Requirement for RORγ in thymocyte survival and lymphoid organ development. Science 2000; 288: 2369-2373.
  • 24. Ivanov I.I., Zhou L., Littman D.R.: Transcriptional regulation of Th17 cell differentiation. Semin. Immunol. 2007; 19: 409-417.
  • 25. Aloisi F., Carè A., Borsellino G. i wsp.: Production of hemolymphopoietic cytokines (IL-6, IL-8, colony-stimulating factors) by normal human astrocytes in response to IL-1 beta and tumor necrosis factor-alpha. J. Immunol. 1992; 149: 2358-2366.
  • 26. Kroenke M.A., Carlson T.J., Andjelkovic A.V., Segal B.M.: IL-12- and IL-23-modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition. J. Exp. Med. 2008; 205: 1535-1541.
  • 27. Kebir H., Kreymborg K., Ifergan I. i wsp.: Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat. Med. 2007; 13: 1173- -1175.
  • 28. Pelus L.M., Horowitz D., Cooper S.C., King A.G.: Peripheral blood stem cell mobilization. A role for CXC chemokines. Crit. Rev. Oncol. Hematol. 2002; 43: 257-275.
  • 29. Samoilova E.B., Horton J.L., Hilliard B. i wsp.: IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: roles of IL-6 in the activation and differentiation of autoreactive T cells. J. Immunol. 1998; 161: 6480-6486.
  • 30. Jacobs C.A., Baker P.E., Roux E.R. i wsp.: Experimental autoimmune encephalomyelitis is exacerbated by IL-1 alpha and suppressed by soluble IL-1 receptor. J. Immunol. 1991; 146: 2983-2989.
  • 31. Ogura H., Murakami M., Okuyama Y. i wsp.: Interleukin-17 promotes autoimmunity by triggering a positive-feedback loop via interleukin-6 induction. Immunity 2008; 29: 628-636.
  • 32. Nowak E.C., Weaver C.T., Turner H. i wsp.: IL-9 as a mediator of Th17-driven inflammatory disease. J. Exp. Med. 2009; 206: 1653-1660.
  • 33. Ivanov I.I., McKenzie B.S., Zhou L. i wsp.: The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006; 126: 1121-1133.
  • 34. Jovanovic D.V., Di Battista J.A., Martel-Pelletier J. i wsp.: IL-17 stimulates the production and expression of proinflammatory cytokines, IL-β and TNF-α, by human macrophages. J. Immunol. 1998; 160: 3513-3521.
  • 35. Sutton C., Brereton C., Keogh B. i wsp.: A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J. Exp. Med. 2006; 203: 1685-1691.
  • 36. Ferrari C.C., Depino A.M., Prada F. i wsp.: Reversible demyelination, blood-brain barrier breakdown, and pronounced neutrophil recruitment induced by chronic IL-1 expression in the brain. Am. J. Pathol. 2004; 165: 1827-1837.
  • 37. Elyaman W., Bradshaw E.M., Uyttenhove C. i wsp.: IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells. Proc. Natl Acad. Sci. USA 2009; 106: 12885-12890.
  • 38. Siffrin V., Radbruch H., Glumm R. i wsp.: In vivo imaging of partially reversible Th17 cell-induced neuronal dysfunction in the course of encephalomyelitis. Immunity 2010; 33: 424-436.
  • 39. Ramgolam V.S., Sha Y., Jin J. i wsp.: IFN-β inhibits human Th17 cell differentiation. J. Immunol. 2009; 183: 5418-5427.
  • 40. El-behi M., Rostami A., Ciric B.: Current views on the roles of Th1 and Th17 cells in experimental autoimmune encephalomyelitis. J. Neuroimmune Pharmacol. 2010; 5: 189-197.
  • 41. Vojdani A., Lambert J.: The role of Th17 in neuroimmune disorders: target for CAM therapy. Part I. Evid. Based Complement. Alternat. Med. 2009 Jul 21.
Document Type
article
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YADDA identifier
bwmeta1.element.psjd-35562d0a-4d0c-4f4a-bda8-73b3143b8d44
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