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Vol. 99. Issue 9.
Pages 701-707 (November 2008)
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Vol. 99. Issue 9.
Pages 701-707 (November 2008)
Original articles
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Effector Function of CLA+ T Lymphocytes on Autologous Keratinocytes in Psoriasis
Función Efectora de Linfocitos T CLA1 Sobre Queratinocitos Autólogos en Psoriasis
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6468
M. Ferrana,
Corresponding author
mferran@imas.imim.es

Correspondence: Servicio de Dermatología, Hospital del Mar, Passeig Marítim, 25-29, 08003 Barcelona, Spain.
, A.M. Giménez-Arnaua, B. Bellosillob, R.M. Pujola, L.F. Santamaría-Babia
a Servicio de Dermatología, Hospital del Mar-IMAS/IMIM, Barcelona, Spain
b Servicio de Anatomía Patológica, Hospital del Mar-IMAS/IMIM, Barcelona, Spain
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Abstract
Background

Cutaneous lymphocyte antigen (CLA) is expressed by a subgroup of memory T cells that exhibit skin homing and are implicated in cutaneous T-cell-mediated diseases.

Material and methods

Expression of genes associated with psoriasis was analyzed in keratinocytes taken from patients and healthy individuals and cultured under different conditions, including activation using supernatants from CLA+ T lymphocytes activated with anti-CD3 and anti-CD28 antibodies.

Results

Keratinocytes from psoriasis patients activated by CLA+ T lymphocytes expressed higher levels of interferon-inducible protein 10, HLA-DR, intercellular cell adhesion molecule 1, and inducible nitric oxide synthase.

Conclusions

Our results suggest that we have developed an in vitro model that will allow analysis of the effector role of CLA+ T lymphocytes on keratinocytes in psoriasis. This model may allow the identification of genes involved in the pathology of psoriasis through induction by CLA+ T lymphocytes.

Key words:
psoriasis
cutaneous lymphocyte antigen
keratinocyte
inducible nitric oxide synthase
Resumen
Introducción

Los linfocitos T CLA+ representan un subgrupo de linfocitos T de memoria con tropismo cutáneo que están implicados en diferentes enfermedades cutáneas mediadas por células T.

Material y métodos

Se estudió la expresión de algunos genes asociados a la psoriasis en queratinocitos de enfermos y sanos cultivados en diferentes condiciones, entre ellas la activación por sobrenadantes de linfocitos T CLA+ activados mediante anti-CD3/anti-CD28.

Resultados

Los queratinocitos psoriásicos activados por linfocitos CLA+ expresan más IP-10, HLA-DR, ICAM-1 e iNOS.

Discusión

Estos resultados sugieren que hemos establecido un modelo in vitro que permite estudiar la función efectora de los linfocitos T CLA+ sobre los queratinocitos en la psoriasis. Este modelo puede permitir la identificación de genes relevantes en la patogenia de la psoriasis al ser inducidos por linfocitos T CLA+.

Palabras clave:
psoriasis
antígeno linfocitario cutáneo
CLA
queratinocito
iNOS
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References
[1.]
L.F. Santamaría-Babi.
CLA (+) T cells in cutaneous diseases.
Eur J Dermatol, 14 (2004), pp. 13-18
[2.]
G.Y. Chen, H. Osada, L.F. Santamaría-Babi, R. Kannagi.
Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes.
Proc Natl Acad Sci USA, 103 (2006), pp. 16894-16899
[3.]
L.F. Santamaría-Babi.
Skin-homing T cells in cutaneous allergic inflammation.
Chem Immunol Allergy, 91 (2006), pp. 87-97
[4.]
A.M. Bowcock, J.G. Krueger.
Getting under the skin: the immunogenetics of psoriasis.
Nat Rev Immunol, 5 (2005), pp. 699-711
[5.]
B.J. Nickoloff, F.O. Nestle.
Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities.
J Clin Invest, 113 (2004), pp. 1664-1675
[6.]
M.A. Lowes, A.M. Bowcock, J.G. Krueger.
Pathogenesis and therapy of psoriasis.
Nature, 445 (2007), pp. 866-873
[7.]
M. Pont-Giralt, A.M. Giménez-Arnau, R.M. Pujol, L.F. Santamaría-Babi.
Circulating CLA(+) T cells from acute and chronic psoriasis patients manifest a different activation state and correlation with disease severity and extension.
J Invest Dermatol, 126 (2006), pp. 227-228
[8.]
O. Boyman, H.P. Hefti, C. Conrad, B.J. Nickoloff, M. Suter, F.O. Nestle.
Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor-alpha.
J Exp Med, 199 (2004), pp. 731-736
[9.]
L.J. Picker, S.A. Michie, L.S. Rott, E.C. Butcher.
A unique phenotype of skin-associated lymphocytes in humans. Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites.
Am J Pathol, 136 (1990), pp. 1053-1068
[10.]
W. Lew, A.M. Bowcock, J.G. Krueger.
Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and «Type 1» inflammatory gene expression.
Trends Immunol, 25 (2004), pp. 295-305
[11.]
L.F. Santamaría Babi, R. Moser, M.T. Pérez Soler, L.J. Picker, K. Blaser, C. Hauser.
Migration of skin-homing T cells across cytokine-activated human endothelial cell layers involves interaction of the cutaneous lymphocyte-associated antigen (CLA), the very late antigen-4 (VLA-4), and the lymphocyte function-associated antigen-1 (LFA-1).
J Immunol, 154 (1995), pp. 1543-1550
[12.]
D. Parent, B.A. Bernard, C. Desbas, M. Heenen, M.Y. Darmon.
Spreading of psoriatic plaques: alteration of epidermal differentiation precedes capillary leakiness and anomalies in vascular morphology.
J Invest Dermatol, 95 (1990), pp. 333-340
[13.]
A. Ragaz, A.B. Ackerman.
Evolution, maturation, and regression of lesions of psoriasis. New observations and correlation of clinical and histologic findings.
Am J Dermatopathol, 1 (1979), pp. 199-214
[14.]
S.C. Davison, A. Ballsdon, M.H. Allen, J.N. Barker.
Early migration of cutaneous lymphocyte-associated antigen (CLA) positive T cells into evolving psoriatic plaques.
Exp Dermatol, 10 (2001), pp. 280-285
[15.]
W.H. Vissers, C.H. Arndtz, L. Muys, P.E. Van Erp, E.M. de Jong, P.C. van de Kerkhof.
Memory effector (CD45RO+) and cytotoxic (CD8+) T cells appear early in the marginal zone of spreading psoriatic lesions in contrast to cells expressing natural killer receptors, which appear late.
Br J Dermatol, 150 (2004), pp. 852-859
[16.]
R. Kunstfeld, S. Lechleitner, M. Groger, K. Wolff, P. Petzelbauer.
HECA-452+ T cells migrate through superficial vascular plexus but not through deep vascular plexus endothelium.
J Invest Dermatol, 108 (1997), pp. 343-348
[17.]
T. Biedermann, C. Schwarzler, G. Lametschwandtner, G. Thoma, N. Carballido-Perrig, J. Kund, et al.
Targeting CLA/Eselectin interactions prevents CCR4-mediated recruitment of human Th2 memory cells to human skin in vivo.
[18.]
Z. Bata-Csorgo, C. Hammerberg, J.J. Voorhees, K.D. Cooper.
Kinetics and regulation of human keratinocyte stem cell growth in short-term primary ex vivo culture. Cooperative growth factors from psoriatic lesional T lymphocytes stimulate proliferation among psoriatic uninvolved, but not normal, stem keratinocytes.
J Clin Invest, 95 (1995), pp. 317-327
[19.]
J.C. Prinz, B. Gross, S. Vollmer, P. Trommler, I. Strobel, M. Meurer, et al.
T cell clones from psoriasis skin lesions can promote keratinocyte proliferation in vitro via secreted products.
Eur J Immunol, 24 (1994), pp. 593-598
[20.]
L.F. Santamaría Babi, L.J. Picker, M.T. Pérez Soler, K. Drzimalla, P. Flohr, K. Blaser, et al.
Circulating allergen-reactive T cells from patients with atopic dermatitis and allergic contact dermatitis express the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen.
J Exp Med, 181 (1995), pp. 1935-1940
[21.]
B. Homey, M.C. Dieu-Nosjean, A. Wiesenborn, C. Massacrier, J.J. Pin, E. Oldham, et al.
Up-regulation of macrophage inflammatory protein-3 alpha/CCL20 and CC chemokine receptor 6 in psoriasis.
J Immunol, 164 (2000), pp. 6621-6632
[22.]
E.J. Kunkel, E.C. Butcher.
Chemokines and the tissue-specific migration of lymphocytes.
Immunity, 16 (2002), pp. 1-4
[23.]
P.W. Cook, M. Piepkorn, C.H. Clegg, G.D. Plowman, J.M. DeMay, J.R. Brown, et al.
Transgenic expression of the human amphiregulin gene induces a psoriasis-like phenotype.
J Clin Invest, 100 (1997), pp. 2286-2294
[24.]
N.G. Singer, R. Mitra, F. Lialios, B.C. Richardson, R.M. Marks, J.M. Pesando, et al.
CD6 dependent interactions of T cells and keratinocytes: functional evidence for a second CD6 ligand on gamma-interferon activated keratinocytes.
Immunol Lett, 58 (1997), pp. 9-14
[25.]
Y. Shimizu, M. Sakai, Y. Umemura, H. Ueda.
Immunohistochemical localization of nitric oxide synthase in normal human skin: expression of endothelial-type and inducibletype nitric oxide synthase in keratinocytes.
J Dermatol, 24 (1997), pp. 80-87
[26.]
A. Sirsjo, M. Karlsson, A. Gidlof, O. Rollman, H. Torma.
Increased expression of inducible nitric oxide synthase in psoriatic skin and cytokine-stimulated cultured keratinocytes.
Br J Dermatol, 134 (1996), pp. 643-648
[27.]
D. Bruch-Gerharz, O. Schnorr, C. Suschek, K.F. Beck, J. Pfeilschifter, T. Ruzicka, et al.
Arginase 1 overexpression in psoriasis: limitation of inducible nitric oxide synthase activity as a molecular mechanism for keratinocyte hyperproliferation.
Am J Pathol, 162 (2003), pp. 203-211
[28.]
I. Arany, M.M. Brysk, H. Brysk, S.K. Tyring.
Regulation of inducible nitric oxide synthase mRNA levels by differentiation and cytokines in human keratinocytes.
Biochem Biophys Res Commun, 220 (1996), pp. 618-622
[29.]
A.D. Ormerod, R. Weller, P. Copeland, N. Benjamin, S.H. Ralston, P. Grabowksi, et al.
Detection of nitric oxide and nitric oxide synthases in psoriasis.
Arch Dermatol Res, 290 (1998), pp. 3-8
[30.]
D. Bruch-Gerharz, K. Fehsel, C. Suschek, G. Michel, T. Ruzicka, V. Kolb-Bachofen.
A proinflammatory activity of interleukin 8 in human skin: expression of the inducible nitric oxide synthase in psoriatic lesions and cultured keratinocytes.
J Exp Med, 184 (1996), pp. 2007-2012
[31.]
C.V. Suschek, O. Schnorr, V. Kolb-Bachofen.
The role of iNOS in chronic inflammatory processes in vivo: is it damagepromoting, protective, or active at all?.
Curr Mol Med, 4 (2004), pp. 763-775
[32.]
M.R. Namazi.
Explaining decreased nitric oxide production in psoriatic lesions: arginase 1 overexpression versus calcitonin gene-related peptide.
Am J Pathol, 163 (2003), pp. 2642
[33.]
N.S. Tekin, N. Ilter, B. Sancak, M.G. Ozden, M.A. Gurer.
Nitric oxide levels in patients with psoriasis treated with methotrexate.
Mediators Inflamm, 2006 (2006), pp. 16043
[34.]
S.V. Kotenko.
The family of IL-10-related cytokines and their receptors: related, but to what extent?.
Cytokine Growth Factor Rev, 13 (2002), pp. 223-240
[35.]
Y.C. Liao, W.G. Liang, F.W. Chen, J.H. Hsu, J.J. Yang, M.S. Chang.
IL-19 induces production of IL-6 and TNF-alpha and results in cell apoptosis through TNF-alpha.
J Immunol, 169 (2002), pp. 4288-4297
[36.]
J. Rømer, E. Hasselager, P.L. Nørby, T. Steiniche, J. Thorn Clausen, K. Kragballe.
Epidermal overexpression of interleu-kin-19 and –20 mRNA in psoriatic skin disappears after short-term treatment with cyclosporine a or calcipotriol.
J Invest Dermatol, 121 (2003), pp. 1306-1311
[37.]
S. Kunz, K. Wolk, E. Witte, K. Witte, W.D. Doecke, H.D. Volk, et al.
Interleukin (IL)-19, IL-20 and IL-24 are produced by and act on keratinocytes and are distinct from classical ILs.
Exp Dermatol, 15 (2006), pp. 991-1004
[38.]
K. Ghoreschi, P. Thomas, S. Breit, M. Dugas, R. Mailhammer, W. van Eden, et al.
Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease.
Nat Med, 9 (2003), pp. 40-46
[39.]
K. Otkjaer, K. Kragballe, A.T. Funding, J.T. Clausen, P.L. Noerby, T. Steiniche, et al.
The dynamics of gene expression of interleukin-19 and interleukin-20 and their receptors in psoriasis.
Br J Dermatol, 153 (2005), pp. 911-918

Study financed by an award from Fundation Salud 2000 for study of clinical immunology of psoriasis (2003).

Copyright © 2008. Academia Española de Dermatología y Venereología and Elsevier España, S.L.
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