Significance of IL-7 and IL-7R in RA and autoimmunity.
Significance of IL-7 and IL-7R in RA and autoimmunity.
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IL-7和IL-7R在类风湿关节炎和自身免疫中的意义
DOI：
10.1016/j.autrev.2022.103120
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发表时间：
2022-07
影响因子：
13.6
通讯作者：
Shahrara, Shiva
中科院分区：
文献类型：
--
作者：
Meyer, Anja;Parmar, Prashant J.;Shahrara, Shiva
虽然IL-7的生理水平对于T细胞增殖、存活和共刺激是必不可少的，但其浓度升高与自身免疫性疾病如风湿性关节炎（RA）相关。RA单核细胞中IL-7和IL-7 R的表达与疾病活动评分和TNF转录相关。TNF刺激可以调节髓样细胞中IL-7分泌和IL-7 R频率，然而，在抗TNF应答患者中仅IL-7 R转录水平下调。RA滑膜组织和液体中IL-7水平升高参与吸引RA单核细胞进入炎症关节并将其重塑为促炎巨噬细胞和成熟破骨细胞。此外，IL-7对RA Th 1细胞分化和IFNγ分泌的扩增可直接引发骨髓IL-7 R表达，从而加剧IL-7介导的关节炎性和侵蚀性印记。同时，IL-7通过扩大RA巨噬细胞和内皮细胞的促血管生成因子的产生来增强关节血管生成。在临床前模型中，阻断IL-7或IL-7 R可以主要通过阻止单核细胞和内皮细胞浸润以及抑制促炎巨噬细胞和Th 1/Th 17细胞分化来有效地损害关节炎症、破骨细胞形成和新血管形成。总之，IL-7/IL-7 R信号传导的中断可以独特地阻断RA髓样细胞和淋巴样细胞之间的串扰，以触发新血管形成。
While physiological levels of IL-7 are essential for T cell proliferation, survival and co-stimulation, its escalated concentration has been associated with autoimmune diseases such as Rheumatoid arthritis (RA). Expression of IL-7 and IL-7R in RA monocytes is linked to disease activity score and TNF transcription. TNF stimulation can modulate IL-7 secretion and IL-7R frequency in myeloid cells, however, only IL-7R transcription levels are downregulated in anti-TNF responsive patients. Elevated levels of IL-7 in RA synovial tissue and fluid are involved in attracting RA monocytes into the inflammatory joints and remodeling them into proinflammatory macrophages and mature osteoclasts. Further, IL-7 amplification of RA Th1 cell differentiation and IFNγ secretion, can directly prime myeloid IL-7R expression and thereby exacerbate IL-7-mediated joint inflammatory and erosive imprints. In parallel, IL-7 accentuates joint angiogenesis by expanding the production of proangiogenic factors from RA macrophages and endothelial cells. In preclinical models, blockade of IL-7 or IL-7R can effectively impair joint inflammation, osteoclast formation, and neovascularization primarily by impeding monocyte and endothelial cell infiltration as well as inhibition of pro-inflammatory macrophage and Th1/Th17 cell differentiation. In conclusion, disruption of IL-7/IL-7R signaling can uniquely intercept the crosstalk between RA myeloid and lymphoid cells in their ability to trigger neovascularization.
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DOI：
10.4049/jimmunol.181.1.225
发表时间：
2008-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bayer AL;Lee JY;de la Barrera A;Surh CD;Malek TR
通讯作者：
Malek TR
影响因子：
3.6
作者：
Cai, Li;Xu, Haiyan;Nie, Hong
通讯作者：
Nie, Hong
DOI：
10.1186/ar320
发表时间：
2001
期刊：
Arthritis research
影响因子：
--
作者：
Toyosaki-Maeda T;Takano H;Tomita T;Tsuruta Y;Maeda-Tanimura M;Shimaoka Y;Takahashi T;Itoh T;Suzuki R;Ochi T
通讯作者：
Ochi T
影响因子：
5.5
作者：
Ayala, JM;Goyal, S;Hanlon, WA
通讯作者：
Hanlon, WA
DOI：
10.1073/pnas.86.15.5923
发表时间：
1989-08-01
影响因子：
11.1
作者：
CHAZEN, GD;PEREIRA, GMB;SHEVACH, EM
通讯作者：
SHEVACH, EM