Article information
Resumen
Las espondiloartritis son un grupo heterogéneo de enfermedades asociadas principalmente al complejo mayor de histocompatibilidad alelo HLA- B 27, y factores ambientales. La evidencia de esos desórdenes reflejan un origen autoinmune mediado por el sistema inmune adaptativo, en donde la composición de las lesiones inflamatorias está representada principalmente por macrófagos activados, linfocitos B y linfocitos T. El fenotipo y naturaleza de esas células T aún no están bien establecidos. Recientes estudios han demostrado que el clásico modelo de las células T CD4 efectoras Th-1/Th-2 en estas patologías debe ser reevaluado y darle espacio a las células Th-17 dentro de las patogenias inflamatorias articulares. Estudios preliminares dirigen la investigación hacia el eje IL-23/IL-17 en espondiloartropatías como una nueva propuesta. Considerar el bloqueo de las moléculas involucradas en esta vía podría ser interesante como nuevos blancos terapéuticos.
Palabras clave:
linfocitos Th-17
IL-17
IL-23
espondiloartritis
artritis inducida
inflamación
Abstract
Spondyloarthritides are a heterogeneous group of diseases which are mainly associated with HLA B 27 and environmental factors. The evidence for these disorders reflects an adaptive immune system-mediated autoimmune origin where inflammatory lesion composition is mainly represented by activated macrophages, B lymphocytes and T lymphocytes. These T-cells phenotype and nature has not been well established. Recent studies have shown that the classical CD4+ Th-1/Th-2 effector-cell model should be reevaluated and Th-17 cells should be introduced in inflammatory joint pathogenesis. Preliminary studies have directed research towards the IL-23/IL-17 axis in spondyloarthropathies as a new proposal. The intervention of the molecules involved in this pathway might be interesting as new therapeutic targets.
Key words:
lymphocyte Th-17
IL-17
IL-23
spondyloarthritis
arthritis induced
inflammation
Full text is only aviable in PDF
Referencias
[1.]
V. Dardalhon, T. Korn, V.K. Kuchroo, A.C. Anderson.
Role of Th1 and Th17 cells in organ-specific autoimmunity.
J Autoimmun, 31 (2008), pp. 252-256
[2.]
M. Essakalli, C. Brick, N. Bennani, N. Benseffaj, S. Ouadghiri, O. Atouf.
The latest TH17 lymphocyte in the family of T CD4+ lymphocytes.
Pathol Biol, (2009),
[3.]
F. Annunziato, L. Cosmi, V. Santarlasci, L. Maggi, F. Liotta, B. Mazzinghi, et al.
Phenotypic and functional features of human Th17 cells.
J Exp Med, 204 (2007), pp. 1849-1861
[4.]
T. Korn, E. Bettelli, M. Oukka, V.K. Kuchroo.
IL-17 and Th17 Cells.
Annu Rev Immunol, 27 (2009), pp. 485-517
[5.]
R. Singh, A. Aggarwal, R. Misra.
Th1/Th17 cytokine profiles in patients with reactive arthritis/undifferentiated spondyloarthropathy.
J Rheumatol, 34 (2007), pp. 2285-2290
[6.]
D. Wendling, J.P. Cedoz, E. Racadot.
Serum and synovial fluid levels of p40 IL12/23 in spondyloarthropathy patients.
Clin Rheumatol, 28 (2009), pp. 187-190
[7.]
M. Veldhoen, R.J. Hocking, C.J. Atkins, R.M. Locksley, B. Stockinger.
TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-Producing T Cells.
Immunity, 24 (2006), pp. 179-189
[8.]
T.A. Wynn.
T(H)-17: a giant step from T(H)1 and T(H)2.
Nat Immunol, 6 (2005), pp. 1069-1070
[9.]
P.R. Mangan, L.E. Harrington, D.B. O’Quinn, W.S. Helms, D.C. Bullard, C.O. Elson, et al.
Transforming growth factor-beta induces development of the TH17 lineage.
Nature, 441 (2006), pp. 231-234
[10.]
I.I. Ivanov, B.S. McKenzie, L. Zhou, C.E. Tadokoro, A. Lepelley, J.J. Lafaille, et al.
The Orphan Nuclear Receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper Cells.
Cells, 126 (2006), pp. 1121-1133
[11.]
L. Wei, A. Laurence, K.M. Elias, J.J. O'Shea.
IL-21 is produced by TH17 cells and drives IL-17 production in a STAT3-dependent manner.
J Biol Chem, 282 (2007), pp. 34605-34610
[12.]
P. Miosecc, T. Korn, V.K. Kuchroo.
Interleukin-17 and type 17 helper T cells.
N Engl J Med, 361 (2009), pp. 888-898
[13.]
T. Korn, E. Bettelli, W. Gao, A. Awasthi, A. Jäger, T.B. Strom, et al.
IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells.
Nature, 448 (2007), pp. 484-487
[14.]
E.K. Deenick, S.G. Tangye.
IL-21: a new player in Th17- cell differentiation.
Immunol Cell Biol, 85 (2007), pp. 503-505
[15.]
G. Layh-Schmitt, R.A. Colbert.
The interleukin-23/interleukin-17 axis in spondyloarthritis.
Curr Opin Rheumatol, 20 (2008), pp. 392-397
[16.]
K. Hirota, H. Yoshitomi, M. Hashimoto, S. Maeda, S. Teradaira, N. Sugimoto, et al.
Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model.
J Exp Med, 204 (2007), pp. 2803-2812
[17.]
G. Page, A. Sattler, S. Kersten, ThielF A., A. Radbruch, P. Miossec.
Plasma cell –like morphology of Th1- cytokine-producing cells associated with the loss of CD3 expression.
Am J Pathol, 164 (2004), pp. 409-417
[18.]
J. Furuzawa-Carballeda, M.I. Vargas-Rojas, A.R. Cabral.
Autoimmune inflammation from the Th17 perspective.
Autoimmun Rev, 6 (2007), pp. 169-175
[19.]
C.A. Murphy, C.L. Langrish, Y. Chen, W. Blumenschein, T. McClanahan, R.A. Kastelein, et al.
Divergent proand antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation.
J Exp Med, 198 (2003), pp. 1951-1957
[20.]
K. Iwanami, I. Matsumoto, Y. Tanaka-Watanabe, A. Inoue, M. Mihara, Y. Ohsugi, et al.
Crucial role of the interleukin-6/interleukin-17 cytokine axis in the induction of arthritis by glucose-6-phosphate isomerase.
Arthritis Rheum, 58 (2008), pp. 754-763
[21.]
P.J. Egan, A. van Nieuwenhuijze, I.K. Campbell, I.P. Wicks.
Promotion of the local differentiation of murine Th17 cells by synovial macrophages during acute inflammatory arthritis.
Arthritis Rheum, 58 (2008), pp. 3720-3729
[22.]
W. Chen, W. Jin, N. Hardegen, K.J. Lei, L. Li, N. Marinos, et al.
Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3.
J Exp Med, 198 (2003), pp. 1875-1886
[23.]
E. Betteli, Y. Carrier, W. Gao, T. Korn, T.B. Strom, M. Oukka, et al.
Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells.
Nature, 441 (2006), pp. 235-238
[24.]
C. Sutton, C. Brereton, B. Keogh, K.H. Mills, E.C. Lavelle.
A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis.
J Exp Med, 203 (2006), pp. 1685-1691
[25.]
S.Y. Hwang, J.Y. Kim, K.W. Kim, M.K. Park, Y. Moon, W.U. Kim, et al.
IL-17 induces production of IL-6 and IL-8 in rheumatoid arthritis synovial fibroblasts via NF- κappaB- and PI3-kinase/Akt-dependent pathways.
Arthritis Res Ther, 6 (2004), pp. 120-128
[26.]
H. Park, Z. Li, X.O. Yang, S.H. Chang, R. Nurieva, Y.H. Wang, et al.
A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17.
Nat Immunol, 6 (2005), pp. 1133-1141
[27.]
F. Fossiez, O. Djossou, P. Chomarat, L. Flores-Romo, S. Ait-Yahia, C. Maat, et al.
T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines.
J Exp Med, 183 (1996), pp. 2593-2603
[28.]
Z. Yao, W.C. Fanslow, M.F. Seldin, A.M. Rousseau, S.L. Painter, M.R. Comeau, et al.
Herpes virus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor.
Immunity, 3 (1995), pp. 811-821
[29.]
M. Chabaud, E. Lubberts, L. Joosten, W. van Den Berg, P. Miossec.
IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis.
Arthritis Res, 3 (2001), pp. 168-177
[30.]
K. Sato.
Th17 cells and rheumatoid arthritis from the standpoint of osteoclast differentiation.
Allergol Int, 57 (2008), pp. 109-114
[31.]
B.W. Kirkham, M.N. Lassere, J.P. Edmonds, K.M. Juhasz, P.A. Bird, C.S. Lee, et al.
Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: a two-year prospective study (the DAMAGE study cohort).
Arthritis Rheum, 54 (2006), pp. 1122-1131
[32.]
K.A. Bush, J.S. Walker, C.S. Lee, B.W. Kirkham.
Cytokine expression and synovial pathology in the initiation and spontaneous resolution phases of adjuvant arthritis: Interleukin-17 expression is upregulated in early disease.
Clin Exp Immunol, 123 (2001), pp. 487-495
[33.]
H. Yamada, Y. Nakashima, K. Okazaki, T. Mawatari, J.I. Fukushi, N. Kaibara, et al.
Th1 but not Th17 cells predominate in the joints of patients with rheumatoid arthritis.
Ann Rheum Dis, 67 (2008), pp. 1299-1304
[34.]
J. Zochling, J. Brandt, J. Braun.
The current concept of spondyloarthritis with special emphasis on undifferentiated spondyloarthritis.
Rheumatology, 44 (2005), pp. 1483-1491
[35.]
D. Wendling, J.P. Cedoz, E. Racadot, G. Dumoulin.
Serum IL-17 BMP-7, and bone turnover markers in patients with ankylosing spondylitis.
Joint Bone Spine, 74 (2007), pp. 304-305
[36.]
L. Melis, B. Vandooren, E. Kruithof, P. Jacques, M. De Vos, H. Mielants, et al.
Systemic levels of IL-23 are strongly associated with disease activity in rheumatoid arthritis but not spondyloarthritis.
Ann Rheum Dis, (2009), pp. 5
[37.]
S. Agarwal, R. Misra, A. Aggarwal.
Interleukin 17 levels are increased in juvenile idiopathic arthritis synovial fluid and induce synovial fibroblasts to produce proinflammatory cytokines and matrix metalloproteinases.
J Rheumatol, 35 (2008), pp. 515-519
[38.]
A. Mahendra, R. Misra, A. Aggarwal.
Th1 and Th17 Predominance in the Enthesitis-related Arthritis Form of Juvenile Idiopathic Arthritis.
J Rheumatol, 36 (2009), pp. 1730-1736
[39.]
C. Jandus, G. Bioley, J.P. Rivals, J. Dudler, D. Speiser, P. Romero.
Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides.
Arthritis Rheum, 58 (2008), pp. 2307-2317
[40.]
H. Shen, J.C. Goodall, J.S. Hill Gaston.
Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis.
Arthritis Rheum, 60 (2009), pp. 1647-1656
[41.]
M.L. DeLay, M.J. Turner, E.I. Klenk, J.A. Smith, D.P. Sowders, R.A. Colbert.
HLA-B27 misfolding and the unfolded protein response augment interleukin-23 production and are associated with Th17 activation in transgenic rats.
Arthritis Rheum., 60 (2009), pp. 2633-2643
Copyright © 2010. Asociación Colombiana de Reumatología
