TAGAP instructs Th17 differentiation by bridging Dectin activation to EPHB2 signaling in innate antifungal response.


  • 影响因子:12.19
  • DOI:10.1038/s41467-020-15564-7
  • 作者列表:"Chen J","He R","Sun W","Gao R","Peng Q","Zhu L","Du Y","Ma X","Guo X","Zhang H","Tan C","Wang J","Zhang W","Weng X","Man J","Bauer H","Wang QK","Martin BN","Zhang CJ","Li X","Wang C
  • 发表时间:2020-04-20

:The TAGAP gene locus has been linked to several infectious diseases or autoimmune diseases, including candidemia and multiple sclerosis. While previous studies have described a role of TAGAP in T cells, much less is known about its function in other cell types. Here we report that TAGAP is required for Dectin-induced anti-fungal signaling and proinflammatory cytokine production in myeloid cells. Following stimulation with Dectin ligands, TAGAP is phosphorylated by EPHB2 at tyrosine 310, which bridges proximal Dectin-induced EPHB2 activity to downstream CARD9-mediated signaling pathways. During Candida albicans infection, mice lacking TAGAP mount defective immune responses, impaired Th17 cell differentiation, and higher fungal burden. Similarly, in experimental autoimmune encephalomyelitis model of multiple sclerosis, TAGAP deficient mice develop significantly attenuated disease. In summary, we report that TAGAP plays an important role in linking Dectin-induced signaling to the promotion of effective T helper cell immune responses, during both anti-fungal host defense and autoimmunity.


: TAGAP基因位点与几种感染性疾病或自身免疫性疾病有关,包括念珠菌血症和多发性硬化症。虽然以前的研究已经描述了TAGAP在T细胞中的作用,但对其在其他细胞类型中的功能知之甚少。在这里,我们报道了TAGAP是Dectin诱导的抗真菌信号和促炎细胞因子在骨髓细胞中产生所必需的。在用Dectin配体刺激后,TAGAP被EPHB2在酪氨酸310处磷酸化,其将近端Dectin诱导的EPHB2活性桥接到下游CARD9-mediated信号通路。白色念珠菌感染期间,小鼠缺乏TAGAP安装缺陷免疫应答,Th17细胞分化受损,真菌负荷较高。类似地,在多发性硬化的实验性自身免疫性脑脊髓炎模型中,TAGAP缺陷小鼠发展为显著减毒的疾病。总之,我们报道了在抗真菌宿主防御和自身免疫过程中,TAGAP在连接Dectin诱导的信号传导和促进有效的T辅助细胞免疫应答中起重要作用。



作者列表:["Apivatthakakul A","Kunavisarut P","Rothova A","Pathanapitoon K"]

METHODS::Purpose: To report on ocular Vogt-Koyanagi-Harada (VKH)-like syndrome under vemurafenib treatment for metastatic melanoma.Design: A case report.Method: Description of clinical and imaging manifestations including fundus photography, fluorescein, and indocyanine green angiography.Results: A 46-year-old Thai female was diagnosed with metastatic melanoma of the skin and had been treated with multiple surgical excisions, radiotherapy, and vemurafenib (initial dose 480 mg orally twice daily, subsequently increased to maximum dose of 960 mg twice daily). After 6 months of vemurafenib use, she complained of bilateral redness and photophobia and was diagnosed with bilateral anterior uveitis, which was topically treated. Two weeks later, her visual acuity (VA) sharply deteriorated to 20/80 and counting fingers. Ocular examination at that stage stronly resembled acute VKH disease. She exhibited intraocular inflammation, and her fundus examination revealed bilateral optic disc swelling and serous retinal detachment. Fluorescein angiogram showed disc leakage and multiple pinpoint hyperfluorescence leakage spots and indocyanine green demonstrated multiple hypofluorescent spots. Oral prednisolone 30 mg/day was commenced while vemurafenib medication was ceased. Three weeks later, her vision improved, and serous retinal detachment subsided. However, her cutaneous melanoma recurred.Conclusions: Vemurafenib, a potential adjunct treatment for metastatic melanoma, was complicated by the development of panuveitis, papillitis, and multiple serous detachments. These ocular symptoms were similar to the presentation of acute VKH syndrome.

翻译标题与摘要 下载文献
作者列表:["Crow YJ","Shetty J","Livingston JH"]

METHODS::Comprehensive reviews of the clinical characteristics and pathogenesis of Aicardi-Goutières syndrome (AGS), particularly its contextualization within a putative type I interferonopathy framework, already exist. However, recent reports of attempts at treatment suggest that an assessment of the field from a therapeutic perspective is warranted at this time. Here, we briefly summarize the neurological phenotypes associated with mutations in the seven genes so far associated with AGS, rehearse current knowledge of the pathology as it relates to possible treatment approaches, critically appraise the potential utility of therapies, and discuss the challenges in assessing clinical efficacy. WHAT THIS PAPER ADDS: Progress in understanding AGS disease pathogenesis has led to the first attempts at targeted treatment. Further rational therapies are expected to become available in the short- to medium-term.

关键词: 暂无
翻译标题与摘要 下载文献
作者列表:["Takayama K","Obata H","Takeuchi M"]

METHODS::Purpose: To report the efficacy of adalimumab in a case of chronic Vogt-Koyanagi-Harada (VKH) disease refractory to conventional corticosteroids and immunosuppressive therapy and complicated by central serous chorioretinopathy (CSC).Case report: A 66-year-old woman diagnosed with VKH was treated with intravenous corticosteroids followed by oral corticosteroids and cyclosporine. However, systemic corticosteroids could not be tapered because of recurrent ocular inflammation and systemic complications (diabetes mellitus, moon face, bone weakness), while CSC appeared in both eyes. A diagnosis of chronic VKH resistant to medications complicated by corticosteroid-induced CSC was made. Systemic corticosteroids and cyclosporine were tapered and adalimumab initiated. Bilateral ocular inflammation and CSC were gradually reduced and visual acuity improved without any adverse effect. Twelve months after starting adalimumab monotherapy, no signs of active VKH and CSC were present.Conclusions: Adalimumab is one of the effective therapeutic options for refractory VKH disease complicated with corticosteroid-induced adverse effects.