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A2.31 Immunisation with type II collagen (CII) alters the IL-23 receptor expression profile compared to naïve conditions
  1. W Razawy1,2,
  2. CH Alves1,2,
  3. PS Asmawidjaja1,2,
  4. AMC Mus1,2,
  5. M Molendijk1,2,
  6. W Dankers1,2,
  7. M Oukka3,4,
  8. VK Kuchroo5,6,
  9. E Lubberts1,2
  1. 1Erasmus MC, University Medical Center, Department of Rheumatology, Rotterdam, The Netherlands
  2. 2Erasmus MC, University Medical Center, Department of Immunology, Rotterdam, The Netherlands
  3. 3Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, USA
  4. 4University of Washington, Department of Immunology, Seattle, USA
  5. 5Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, USA
  6. 6Broad Institute of MIT and Harvard, Cambridge, USA

Abstract

Background and objectives Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterised by synovial infiltration of pro-inflammatory cells. In RA, the interleukin-23/17A (IL-23/IL-17A) pathway plays a central role. While in human RA increased IL-23 levels correlate with higher disease activity, IL-23deficient mice are protected against collagen induced arthritis.

Under naïve conditions, it was shown that IL-23 receptor (IL-23R) positivecells were mainly located in the lymph nodes (LNs), but not in the spleens of IL-23R GFP-reporter mice. While these cells were mainly composed of T cells, macrophages and dendritic cells (DCs), no IL-23R expression was found on CD8+ T cells, B cells or NK cells. However, since IL-23R expression can be altered in an inflammatory condition, we aimed to analyse expression of IL-23R on immune cells in lymphoid tissues of type II collagen (CII) immunised mice.

Materials and methods IL-23R GFP-reporter mice and littermate wild type controls were immunised with 100 µg chicken type II collagen in complete Freund’s adjuvant. After 10 days, LNs and spleens of mice were harvested and IL-23R expressing cell types were analysed using flow cytometry.

In addition, splenocytes of IL-23R GFP-reporter mice were cultured overnight with IL-23, in order to assess their responsiveness.

Results In contrast to naïve mice, IL-23R expression was detected on B cells and CD8+ T cells in LNs of CII immunised mice. While T cells were the most prominent IL-23R-expressing cell type in the LNs, DCs formed the main IL-23R+ population in the spleens. Furthermore, IL-23R expression was found on splenic B cells. Within the T cell population, γδ T cells form the largest IL-23R+ cell type in both the LNs and spleens. In vitro, splenocytes of IL-23R GFP-reporter mice respond to IL-23 by upregulating IL-23R gene expression.

Conclusions In contrast to naïve mice, IL-23R+ cells such as DCs, B cells and γδ T cells were detected in the spleens of CII immunised mice. Furthermore, γδ T cells, B cells and CD8+ T cells express IL-23R in the LNs. These data suggest that immunisation with CII alters the IL-23R expression profile compared to naïve conditions.

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