Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746756
Title: Defining the T cell and innate lymphoid cell signature in childhood arthritis
Author: Lom, Hannah R. G.
ISNI:       0000 0004 7225 8641
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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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.
Supervisor: Wedderburn, L. ; Bajaj-Elliott, M. ; Ioannou, J. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.746756  DOI: Not available
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