Interleukin (IL)-9/IL-9R axis drives γδ T cells activation in psoriatic arthritis patients
Interleukin (IL)-9/IL-9R axis drives γδ T cells activation in psoriatic arthritis patients
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DOI：
10.1111/cei.12853
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发表时间：
2016-12-01
影响因子：
4.6
通讯作者：
Triolo, G.
中科院分区：
文献类型：
--
作者：
Guggino, G.;Ciccia, F.;Triolo, G.
细胞因子如肿瘤坏死因子（TNF）-、白细胞介素（IL）-12、干扰素（IFN）-、IL-23和最近的IL-9已涉及银屑病和银屑病关节炎（PsA）中炎症的起始/维持。在本研究中，我们的目的是表征的作用，T细胞在外周血和滑膜液的PsA患者，并探讨他们在体外刺激抗原或细胞因子（IL-9和IL-23）的反应。通过流式细胞术分析从外周血单核细胞和滑液中分离的T细胞，以评估表型和细胞因子产生。逆转录-聚合酶链反应（RT-PCR）检测IL-23 R和IL-9 R基因表达。外周血单核细胞（PBMC）、分选的T细胞和细胞系也在体外用异戊烯焦磷酸（IPP）、重组IL-9或重组IL-23刺激。我们的研究结果表明，在未经治疗的PsA患者的外周血和滑膜中，具有主要效应记忆表型的T细胞的扩增，其在用抗TNF-或抗IL-12/IL-23 R单克隆抗体（mAb）治疗后显著逆转。此外，在PsA患者中，T细胞活化主要由IL-9/IL-9 R相互作用驱动，而不仅仅是由IL-23/IL-23 R驱动。这些发现共同表明T细胞和IL-9作为PsA发病机制中的新参与者。
Cytokines such as tumour necrosis factor (TNF)-, interleukin (IL)-12, interferon (IFN)-, IL-23 and, more recently, IL-9, have been implicated in the initiation/maintenance of inflammation in psoriasis and psoriatic arthritis (PsA). In the present study we aimed to characterize the role of T cells in peripheral blood and synovial fluid of PsA patients and to investigate their response to in-vitro stimulation with antigen or cytokines (IL-9 and IL-23). T cells isolated from peripheral blood mononuclear cells and synovial fluid were analysed by flow cytometry to evaluate the phenotype and cytokine production. IL-23R and IL-9R gene expression were also evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Peripheral blood mononuclear cells (PBMC), sorted T cells and cell lines were also stimulated in vitro with isopentenyl pyrophosphate (IPP), recombinant IL-9 or recombinant IL-23. Our results show an expansion of T cells with a predominant effector memory phenotype in peripheral blood and synovium of untreated PsA patients, which reverses significantly after treatment with anti-TNF- or anti-IL-12/IL-23R monoclonal antibodies (mAbs). Moreover, in PsA patients T cells activation is driven prevalently by IL-9/IL-9R interaction, and not only by IL-23/IL-23R. Together these findings indicate T cells and IL-9 as new players in the pathogenesis of PsA.