Production of Interleukin 8 by Circulating CLA+ T Cells With Skin Tropism in Patients With Psoriasis and in Healthy Controls

Ferran, M.; Galván, A.B.; Giménez-Arnau, A.; Pujol, R.M.; Santamaría-Babia, L.F.

doi:10.1016/S1578-2190(10)70601-6

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Abstract

Background

Psoriasis is an immune-mediated disease typically associated with cutaneous neutrophilic infiltration and Munro microabscesses. Interleukin (IL)-8 is one of the main neutrophil-attracting chemokines. Although keratinocytes have traditionally been considered to be the principal source of IL-8 in psoriasis, we present data that suggest that cutaneous lymphocyte associated antigen CLA+ T lymphocytes synthesize this cytokine.

Material and methods

Six patients with psoriasis and 6 healthy controls were studied. Immunomagnetic separation was used to isolate CLA+ and CLA− T lymphocytes and IL-8 and interferon (IFN)-γ production was quantified for each cell subpopulation using enzyme-linked immunosorbent assay. Finally, gene expression of IL-8 was analyzed by reverse transcriptase-polymerase chain reaction.

Results

CLA+ and CLA− T lymphocytes from patients with psoriasis and from controls showed a significantly increased production of IFN-γ when activated, whereas only activated CLA+ T lymphocytes (from patients and controls) synthesized IL-8. The higher level of expression of IL-8 and IFN-γ by CLA+ T lymphocytes in comparison to CLA− cells was confirmed.

Discussion

Previous studies have confirmed IL-8 production by T lymphocytes in inflammatory skin diseases with neutrophil-rich infiltrates, such as acute generalized exanthematous pustulosis, Behçet disease, and pustular psoriasis. We have confirmed the role of the subset of T lymphocytes with skin tropism (CLA+) in IL-8 production in nonpustular psoriasis.

Keywords:

Psoriasis

T lymphocyte

CLA

Neutrophil

IL-8

Resumen

Introducción

La psoriasis es una enfermedad mediada inmunológicamente, de causa desconocida, que característicamente presenta infiltración cutánea por polimorfonucleares neutrófilos y microabscesos de Munro. La interleucina (IL)-8 es una de las principales quemocinas atrayentes de los polimorfonucleares neutrófilos. Aunque la producción de IL-8 en psoriasis se ha atribuido principalmente al queratinocito, presentamos datos que apoyan la producción de esta por los linfocitos T antígeno de linfocito cutáneo (CLA)+.

Material y métodos

Se incluyeron 6 pacientes con psoriasis y 6 sanos. Mediante técnicas de separación inmunomagnética se aislaron los linfocitos T CLA+ y CLA-. Se cuantificó la producción de IL-8 e IFNγ de cada subpoblación celular a través de un ELISA. Finalmente, se analizó su expresión génica mediante reacción en cadena de la polimerasa a tiempo real.

Resultados

Tanto los linfocitos T CLA+ como CLA-, de controles y pacientes con psoriasis, aumentaban significativamente la producción de IFNγ cuando eran activados, mientras que sólo los linfocitos T CLA+ activados, tanto de controles como de sujetos con psoriasis, producían IL-8. Se confirmó la expresión preferente de IL-8 e IFNγ en linfocitos T CLA+ respecto de CLA-.

Discusión

Estudios previos han demostrado la producción de IL-8 por linfocitos T en dermatosis inflamatorias ricas en neutrófilos, tales como la pustulosis exantemática aguda generalizada, la enfermedad de Behçet y la psoriasis pustulosa. Nosotros hemos confirmado el papel del subgrupo de linfocitos T con tropismo cutáneo (CLA+) en la producción de IL-8 en la psoriasis no pustulosa.

Palabras clave:

Psoriasis

Linfocitos T

Antígeno de linfocito cutáneo

Neutrófilos

IL-8

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