Brief report: Innate lymphoid cells and T-cells contribute to the IL-17A signature detected in the synovial fluid of patients with Juvenile Idiopathic Arthritis

Research output: Contribution to journalArticlepeer-review

Authors

  • Elizabeth Rosser
  • Hannah Lom
  • Chantal Duurland
  • Mona Bajaj-Elliott
  • Lucy R. Wedderburn

Colleges, School and Institutes

Abstract

Objective: Evidence suggests that aberrant function of innate lymphoid cells (ILC), whose functional and transcriptional profile overlap with T helper (Th) cell subsets, contribute to immune-mediated pathologies. To date, analysis of Juvenile Idiopathic Arthritis (JIA) immune-pathology has concentrated on the contribution of CD4+ T-cells; we have previously identified an expansion of Th17 cells within the synovial fluid (SF) of JIA patients. Here, we extend this analysis to investigate a role for ILC and other IL-17 producing T-cell subsets.


Methods: ILC and CD3+ T-cell subsets were defined in peripheral blood mononuclear cells (PBMC) (healthy adult, healthy child and JIA patients) and JIA SF mononuclear cells (SFMC) using flow cytometry. Defined subsets in SFMC were correlated with clinical measures including physician’s visual analogue scale (VAS), active joint count and erythrocyte sedimentation rate (ESR). Transcription factor and cytokine profiles of sorted ILC were assessed by qPCR.


Results: Group 1 ILC (ILC1), NKp44-group 3 ILC (NCR-ILC3) and NKp44+group 3 ILC (NCR+ILC3) were enriched in the JIA-SFMC compared to PBMC, which corresponded with an increase in transcripts for TBX21, IFNG and IL17A. Of the ILC subsets, NCR-ILC3 frequency in JIA-SFMC displayed the strongest positive association with clinical measures which was mirrored by an expansion in IL-17A+CD4+, IL- 17A+CD8+ and IL-17A+γδ T-cells.


Conclusion: We demonstrate that the strength of the IL-17A signature in JIA-SFMC is determined by multiple lymphoid cell-types, including NCR-ILC3, IL-17A+CD4+, IL-17A+CD8+ and IL-17A+γδ T-cells. These observations may have important implications for the development of stratified therapeutics.

Details

Original languageEnglish
JournalArthritis and Rheumatology
Early online date22 Oct 2018
Publication statusE-pub ahead of print - 22 Oct 2018