CD4+ CCR6+ T cells, but not γδ T cells, are important for the IL-23R-dependent progression of antigen-induced inflammatory arthritis in mice.,European Journal of Immunology

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CD4+ CCR6+ T cells, but not γδ T cells, are important for the IL-23R-dependent progression of antigen-induced inflammatory arthritis in mice.
European Journal of Immunology ( IF 4.5 ) Pub Date : 2019-11-28 , DOI: 10.1002/eji.201948112
Wida Razawy _{1,

2} , Patrick S Asmawidjaja _{1,

2} , Anne-Marie Mus _{1,

2} , Nazike Salioska _{1,

2} , Nadine Davelaar _{1,

2} , Nicole Kops ₃ , Mohamed Oukka _{4,

5} , C Henrique Alves _{1,

2} , Erik Lubberts _{1,

2}

Affiliation

IL-23 plays an important role in the development of arthritis and the IL-23 receptor (IL-23R) is expressed on different types of T cells. However, it is not fully clear which IL-23R+ T cells are critical in driving T cell-mediated synovitis. We demonstrate, using knock-in IL-23R-GFP reporter (IL-23RGFP/+ ) mice, that CD4+ CCR6+ T cells and γδ T cells, but not CD8+ T cells, express the IL-23R(GFP). During early arthritis, IL-23R(GFP)+ CD4+ CCR6+ T cells, but not IL-23R(GFP)+ γδ T cells, were present in the inflamed joints. IL-23RGFP/+ mice were bred as homozygotes to obtain IL-23RGFP/GFP (IL-23R deficient/IL-23R-/- ) mice, which express GFP under the IL-23R promotor. Arthritis progression and joint damage were significantly milder in IL-23R-/- mice, which revealed less IL-17A+ cells in their lymphoid tissues. Surprisingly, IL-23R-/- mice had increased numbers of IL-23R(GFP)+ CD4+ CCR6+ and CCR7+ CD4+ CCR6+ T cells in their spleen compared to WT, and IL-23 suppressed CCR7 expression in vitro. However, IL-23R(GFP)+ CD4+ CCR6+ T cells were present in the synovium of IL-23R-/- mice at day 4. Finally, adoptive transfer experiments revealed that CD4+ CCR6+ T cells and not γδ T cells drive arthritis progression. These data suggest that IL-23R-dependent T cell-mediated synovitis is dependent on CD4+ CCR6+ T cells and not on γδ T cells.

中文翻译：

CD4 + CCR6 + T细胞（而不是γδT细胞）对于小鼠IL-23R依赖性抗原诱导的炎性关节炎的进展很重要。

IL-23在关节炎的发展中起重要作用，并且IL-23受体（IL-23R）在不同类型的T细胞上表达。但是，尚不清楚哪种IL-23R + T细胞在驱动T细胞介导的滑膜炎中起关键作用。我们证明，使用敲入的IL-23R-GFP报告基因（IL-23RGFP / +）小鼠，CD4 + CCR6 + T细胞和γδT细胞，而不是CD8 + T细胞表达IL-23R（GFP）。在早期关节炎期间，发炎的关节中存在IL-23R（GFP）+ CD4 + CCR6 + T细胞，但没有IL-23R（GFP）+γδT细胞。将IL-23RGFP / +小鼠作为纯合子进行繁殖，以获得在IL-23R启动子下表达GFP的IL-23RGFP / GFP（IL-23R缺陷型/ IL-23R-/-）小鼠。IL-23R-/-小鼠的关节炎进展和关节损伤明显较轻，这表明淋巴组织中的IL-17A +细胞较少。出奇，与WT相比，IL-23R-/-小鼠脾脏中的IL-23R（GFP）+ CD4 + CCR6 +和CCR7 + CD4 + CCR6 + T细胞数量增加，并且IL-23在体外抑制了CCR7表达。然而，在第4天，IL-23R-/-小鼠滑膜中存在IL-23R（GFP）+ CD4 + CCR6 + T细胞。最后，过继转移实验表明CD4 + CCR6 + T细胞而非γδT细胞驱动关节炎的发展。这些数据表明IL-23R依赖的T细胞介导的滑膜炎依赖于CD4 + CCR6 + T细胞，而不依赖于γδT细胞。过继转移实验表明，CD4 + CCR6 + T细胞而非γδT细胞驱动关节炎的发展。这些数据表明IL-23R依赖的T细胞介导的滑膜炎依赖于CD4 + CCR6 + T细胞，而不依赖于γδT细胞。过继转移实验表明，CD4 + CCR6 + T细胞而非γδT细胞驱动关节炎的发展。这些数据表明IL-23R依赖的T细胞介导的滑膜炎依赖于CD4 + CCR6 + T细胞，而不依赖于γδT细胞。

更新日期：2019-11-29

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