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
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
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P168 患有幼年特发性关节炎的年轻人体内丰富的组织驻留 CD8 记忆 T 细胞群概括了炎症性关节炎发作小鼠模型的发现
DOI：
10.1093/rheumatology/keac133.167
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发表时间：
2022
期刊：
影响因子：
5.5
通讯作者：
Bolton C
中科院分区：
文献类型：
--
作者：
Bolton C
背景/目的幼年特发性关节炎（JIA）发病和发作期间的不对称关节炎症与疾病中的常驻细胞群和微环境有关。已经从鼠模型中鉴定出持久的CD 8+组织驻留细胞群，其能够使关节朝向夸大的炎症反应，其抵抗全身性治疗。这些组织驻留的CD 8+记忆T细胞（TRM）的克隆扩增富集群体已经在患有JIA的儿童的滑液中鉴定。银屑病关节炎的成年人（n = 3）和健康成年志愿者的血液（n = 4）。结果大量T淋巴细胞和髓样细胞群在对应于关节炎亚型的滑液单核细胞（与配对的PBMC相比）中表现出富集。滑膜JIA样本中平均2.98%的T细胞具有CD 69 +ITGAE+ CD 8A+组织驻留特征，而配对JIA PBMC中平均为0.37%，其他样本类型中平均为0.24%（P <0.00001，vs滑膜银屑病样本）。这些细胞概括了先前观察到的组织驻留CD 8 + T细胞的特征，包括转录因子RUNX 3、颗粒酶和FABP 5脂肪酸转运蛋白的高表达。在小鼠模型中，趋化因子CCL 5对于白细胞募集介导炎症发作至关重要，并且实际上，JIA滑液样品在TRM中表现出更强的CCL 5表达。此外，与外周血相比，参与CD 8+组织驻留T细胞调节和维持的细胞因子的转录物在JIA滑膜样品中特异性富集，包括IL-15、IL-12、IFN-γ;这表明环境有利于该种群的持续存在。结论我们证实了之前-描述了JIA患者滑液中的细胞群，并鉴定了具有组织驻留特征的CD 8 T细胞的富集。需要进一步的研究来确定这些人群的意义或功能意义。博尔顿：没有。里奇-格里芬：没有。没有。布朗：没有。Al-Mossawi：无。克罗夫特：没有。Wedderburn：Consultancies; L.R.W.从辉瑞公司收到了与这项工作无关的咨询费。赠款/研究支助; L.R.W.宣布AbbVie、GSK、Pfizer、Sobi和UCB支持CLUSTER联盟。
Background/AimsAsymmetrical 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.MethodsWe 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).ResultsA 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.ConclusionWe 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.DisclosureC. 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.