Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


IL-23 Suppresses IL-22 Levels and AHR Expression in Human CCR6 Memory T Cells.

Cornelissen,  Ferry, Piet van Hamburg,  Jan, Davelaar,  Nadine, Asmawidjaja,  Patrick, Mus,  Anne-Marie, Lubberts,  Erik

Background:

Human CCR6+ T helper (Th) cells were shown to preferentially express the cytokines IL-17A and IL-22 (1). Recently, it became clear that within the CCR6+ Th cell population, cells are present which exclusively expressed IL-22 (2, 3). Although IL-23 and IL-1b are involved in the differentiation of naïve T cells towards effector CCR6+ Th cells (4), their role in the regulation of IL-17A and IL-22 expression by effector CCR6+ Th cells is unknown.

Objective:

To investigate the role of IL-23 and IL-1b on the expression of Th17 specific cytokines by human memory CCR6+ Th cells.

Methods:

CD4+CD45RO+CCR6+ T cells were FACS sorted from PBMC obtained from healthy individuals. These cells were cultured in the absence or presence of IL-23, IL-1b or the combination of IL-23+IL-1b. After culture, intracellular cytokine stainings for IL-17A, IL-22, and IFN-gamma were analyzed by flow cytometry. Cytokine levels of IL-17A, IL-22, and IFN-gamma were determined in the supernatant by enzyme-linked immunosorbant assay (ELISA). Semi-Quantitative RT-PCR was performed to analyse gene transcription of genes involved in Th differentiation and or function.

Results:

IL-23 had no effect on the percentage of IL-1259-positive and IFN-gamma-positive cells. However, IL-23 in contrast to IL-1beta significantly decreased the percentage of IL-1259-positive CCR6+ memory T cells. This was mainly due to a significant reduction in the proportion of IL-22+IL-17A- and IL-22+IFN-gamma- T cells. In line with this, significantly lower IL-22 levels were found in the supernatant of CCR6+ T cells incubated with IL-23 and significantly lower expression of the transcription factor aryl-hydrocarbon receptor (AhR) in these cells. In contrast to IL-23, IL-1beta increased the percentage of both IL-17A-positive and IFN-gamma-positive CCR6+ T cells. However, the combination of IL-23/IL-1beta significantly and specifically increased the percentage of IL-17A+IL-1259- and IL-17A+IFN-gamma- compared to IL-1beta alone, although the suppressive effect on IL-1259-positive cells was not increased by this combination compared to IL-23 alone. Significant higher levels of IL-17A but also IFN-gamma were detected after incubation with IL-23/IL-1beta compared to IL-1beta alone. This latter may be due to an increase in IL-17A+IFN-gamma+ double positive CCR6+ memory T cells by IL-23/IL-1beta.

Conclusion:

These data revealed that IL-23 specifically suppresses a Th22-like phenotype in CCR6+ memory T cells resulting in lower IL-22 levels and reduced AhR expression. Adding IL-1beta to IL-23 resulted in a specific increase of a Th17/IL-17A-like phenotype in CCR6+ memory T cells resulting in higher levels of IL-17A. However, the total IFN-gamma level was increased by IL-23/IL-1beta as well. These data suggest an important role for IL-23 in combination with IL-1beta in the regulation of human IL-1259-positive and IL-1259-positive memory T helper cells.

References:

1.Annunziato, F et al.J Exp Med 2007.

2.Trifari, S et al.Nat Immunol 2009;10(8):864–71.

3.Duhen, T et al.Nat Immunol 2009;10(8):857–63.

4.Wilson, NJ et al.Nat Immunol 2007;8(9):950–7.

To cite this abstract, please use the following information:
Cornelissen, Ferry, Piet van Hamburg, Jan, Davelaar, Nadine, Asmawidjaja, Patrick, Mus, Anne-Marie, Lubberts, Erik; IL-23 Suppresses IL-22 Levels and AHR Expression in Human CCR6 Memory T Cells. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1259
DOI: 10.1002/art.29025

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