June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
IL-10 expression by Th17 cells correlates with their response to glucocorticoids
Author Affiliations & Notes
  • Philippa J P Lait
    School of Clinical Sciences, University of Bristol, Bristol, United Kingdom
    National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology, Bristol, United Kingdom
  • Lauren P Schewitz-Bowers
    School of Clinical Sciences, University of Bristol, Bristol, United Kingdom
    National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology, Bristol, United Kingdom
  • Emily Louisa Williams
    School of Clinical Sciences, University of Bristol, Bristol, United Kingdom
    National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology, Bristol, United Kingdom
  • Ester Carreno
    University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom
  • Andrew D Dick
    School of Clinical Sciences, University of Bristol, Bristol, United Kingdom
    National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology, Bristol, United Kingdom
  • Richard W J Lee
    School of Clinical Sciences, University of Bristol, Bristol, United Kingdom
    National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology, Bristol, United Kingdom
  • Footnotes
    Commercial Relationships Philippa Lait, None; Lauren Schewitz-Bowers, None; Emily Williams, None; Ester Carreno, None; Andrew Dick, None; Richard Lee, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 866. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Philippa J P Lait, Lauren P Schewitz-Bowers, Emily Louisa Williams, Ester Carreno, Andrew D Dick, Richard W J Lee; IL-10 expression by Th17 cells correlates with their response to glucocorticoids. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):866.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: We have previously shown that CD4+ T cells from steroid refractory (SR) uveitis patients demonstrate both increased IL-17 expression and a failure to up-regulate IL-10 in response to glucocorticoids; leading to a significantly reduced ratio of IL-10 to IL-17 in CD4+ cells from these patients. Hence, due to the relationship between these two cytokines and the clinical SR uveitis phenotype, we sought to determine the capacity of the synthetic glucocorticoid dexamethasone (Dex) to up-regulate IL-10 in Th17 cells and how production of IL-10 from these cells affects their response to Dex.

Methods: All experiments used blood from healthy donors (N=4). CD4+ T cells were isolated and cultured with anti CD3/CD28 microbeads and 1x10-6M Dex for 4 days. Post culture, Dex induced IL-10 cells were isolated using capture antibodies (Miltenyi Biotech) and sorted (BD influx). Their suppression of CD4+CD25- effector cells was functionally assessed in a standard proliferation assay. Similarly, Th1 and Th17 CD4+ T cells were isolated on the basis of differential expression of CXCR3, CCR4, CCR6 and CD161 and cultured as described. On day 4, intracellular IL-17, IFNγ and IL-10 expression was determined by flow cytometry (BD, LSRII). To assess the effects of IL-10 on suppression by Dex, sorted Th1 and Th17 cells were cultured with IL-2 and autologous irradiated APCs for 14 days, after which intracellular cytokine expression was determined by flow cytometry. Cells were then cultured with 1x10-6M Dex for 24hours and proliferation was quantified using tritiated thymidine incorporation.

Results: Dex induced IL-10+ CD4+ T cells exhibited functional suppression of CD4+CD25- cells (1 Treg:15 effector cell ratio). Both Th17 and Th1 cells were able to up-regulate IL-10 expression after culture with Dex. However, the suppression of proliferation by Dex in Th17 cells correlated positively with the level of IL-10 in these cells.

Conclusions: IL-10 and IL-17 are key cytokines involved in the clinical SR phenotype. In normal volunteers Dex up regulates IL-10 in CD4+ T cells and these cells are functionally suppressive. Further, in Th17 cells from normal volunteers, Dex induces increased IL-10 expression and expression of IL-10 in this cell subset correlates with Dex mediated suppression of proliferation suggesting this may function as a negative feedback mechanism to curb immune responses.<br />

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×