Details

Autor(en) / Beteiligte

• Bolton, Chrissy
• Rich-Griffin, Charlotte
• Dendrou, Calliope
• Brown, Chrysothemis
• Al-Mossawi, Hussein
• Croft, Adam
• Wedderburn, Lucy

Titel

P168 An enriched population of tissue-resident CD8 memory T cells in young people with juvenile idiopathic arthritis recapitulate findings from mouse models of inflammatory arthritis flares

Ist Teil von

• Rheumatology (Oxford, England), 2022-04, Vol.61 (Supplement_1)

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract Background/Aims Asymmetrical joint inflammation at presentation and during flares of juvenile idiopathic arthritis (JIA) implicates resident cell populations and the microenvironment in disease. Persistent CD8+ tissue-resident cell populations have been identified from murine models, capable of priming the joint towards an exaggerated inflammatory response, which resist systemic treatment. Clonally-expanded enriched populations of these tissue-resident CD8+ memory T cells (TRM) have been identified in synovial fluid of children with JIA. Methods We integrate and compare scRNA-seq findings from paired synovial fluid mononuclear cells and blood mononuclear cell (PBMC) samples from children with oligoarticular JIA (n = 2), adults with psoriatic arthritis (n = 3) and blood from healthy adult volunteers (n = 4). Results A number of T lymphocyte and myeloid cell populations demonstrated enrichment amongst synovial fluid mononuclear cells (compared to paired PBMCs) that corresponded across arthritic subtypes. A mean of 2.98% of T cells in synovial JIA samples had the CD69+ITGAE+CD8A+ tissue-resident signature compared to a mean of 0.37% in paired JIA PBMCs and 0.24% in other sample types (P <.00001, vs synovial psoriatic samples). These cells recapitulated previously observed traits of tissue-resident CD8+ T cells, including high expression of transcription factor RUNX3, granzymes and the FABP5 fatty acid transporter. In mouse models the chemokine CCL5 was critical for leukocyte recruitment to mediate inflammatory flares and indeed, JIA synovial fluid samples exhibited stronger expression of CCL5 in TRM. Additionally, transcripts for cytokines involved in CD8+ tissue-resident T cell regulation and maintenance were specifically enriched in JIA synovial samples compared to peripheral blood, including IL-15, IL-12, IFN-γ; suggesting an environment conducive to the persistence of this population. Conclusion We confirm the existence of previously-described cell populations in synovial fluid from JIA patients and identify the enrichment of CD8 T cells with a tissue-resident signature. Further study is required to identify the significance or functional implications of these populations. Disclosure C. Bolton: None. C. Rich-Griffin: None. C. Dendrou: None. C. Brown: None. H. Al-Mossawi: None. A. Croft: None. L. Wedderburn: Consultancies; L.R.W. receieved a consultancy fee from Pfizer unrelated to this work. Grants/research support; L.R.W. declares support from AbbVie, GSK, Pfizer, Sobi, and UCB to the CLUSTER Consortium.