UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Defining the T cell and innate lymphoid cell signature in childhood arthritis

Lom, Hannah RG; (2017) Defining the T cell and innate lymphoid cell signature in childhood arthritis. Doctoral thesis , UCL (University College London). Green open access

[thumbnail of Hannah Lom FINAL THESIS.pdf]
Preview
Text
Hannah Lom FINAL THESIS.pdf

Download (15MB) | Preview

Abstract

Pathogenesis of juvenile idiopathic arthritis (JIA) is linked to the IL-23/IL-17 axis. This is of particular interest as new biological drugs targeting this pathway have been developed and may prove a useful treatment. Increased IL-17+CD4+ T cells have been reported in the joints of patients with JIA, but less is known about IL-17 production from other cell types. Innate lymphoid cells (ILC) bridge innate and adaptive immune systems and are sub-divided into 3 types (1,2 and 3), which mirror CD4+T- cell subsets. This thesis aimed to investigate T cell and ILC contribution to the disease phenotype in the joints of patients with JIA. Using a combination of flow cytometry techniques along with multiplex cytokine analysis, qPCR and culture assays this study has assessed the immune phenotype of patients with JIA. Significant enrichments of IL-17A+ CD4+, CD8 and γδ T cells were observed in the synovial fluid of patients compared to blood, which correlated with disease severity. In parallel, a significant difference was seen between relative proportions and functionality of ILC subpopulations in the synovial fluid of patients compared to blood. IL17+ILC3 and IL-22+ILC3 were significantly enriched at the inflamed site. These two ILC3 populations were negatively correlated suggesting interplay between the two groups. Additionally, IL-17+ILC3 were associated with more severe disease. Further exploration of immune cells found a significant enrichment of myeloid DC (mDC), which strongly correlated with IL-22+ILC3 at the inflamed site. It was shown that synovial mDC produce retinoic acid which may contribute to skewing of ILC populations. These data suggest a strong IL-17A signature in JIA patients, which extends beyond the T cell compartment. Therefore, therapies targeting the IL-17/IL-23 axis could also attenuate ILC populations within the inflamed joint. Finally, these data suggest that IL22+ILC3 populations are induced by mDC and may be protective in disease.

Type: Thesis (Doctoral)
Title: Defining the T cell and innate lymphoid cell signature in childhood arthritis
Event: UCL
Open access status: An open access version is available from UCL Discovery
Language: English
Keywords: Innate Lymphoid Cells, T cells, Juvenile Idiopathic Arthritis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1570572
Downloads since deposit
208Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item