Resolution of Autoimmune Uveitis Requires CCL20-Dependent Regulatory T Cells

IF 4.5 3区 医学 Q2 IMMUNOLOGY
John Dostal, Kayleigh Peters, Trisha McDonald, Darren J. Lee
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引用次数: 0

Abstract

Uveitis is a leading cause of blindness worldwide and regulatory T cells inversely correlate with uveitis. CCL20 is the chemokine that attracts cells expressing CCR6 and has been shown to be expressed on Tregs. Uveitis patients have a reduced capacity to generate CCR6-expressing Tregs. Using the experimental autoimmune uveitis (EAU) model we examined the effect of a CCL20 deficiency on EAU resolution and the induction and function of Tregs. This report demonstrates that a deficiency in CCL20 delays the resolution of EAU and inhibits the induction of Tregs associated with EAU resolution (post-EAU Tregs). Importantly, a CCL20 deficiency does not impact the capacity of post-EAU Tregs to suppress EAU. The impact of these observations is that if the deficiency preventing the induction of ocular Tregs can be bypassed these Tregs will still be able to function to provide lasting remission of uveitis. This study is the first demonstration that CCL20 is needed for the timely resolution of EAU, that it is required for the generation of post-EAU Tregs, and that CCL20 is not required for post-EAU Tregs to suppress disease, that is, CCL20 is needed for timely resolution of EAU and Treg induction but not function.

自身免疫性葡萄膜炎的解决需要依赖ccl20的调节性T细胞
葡萄膜炎是全球失明的主要原因,调节性T细胞与葡萄膜炎呈负相关。ccr20是吸引表达CCR6的细胞的趋化因子,已被证明在treg上表达。葡萄膜炎患者产生表达ccr6的treg的能力降低。利用实验性自身免疫性葡萄膜炎(EAU)模型,我们研究了CCL20缺乏对EAU溶解和Tregs诱导和功能的影响。该报告表明,缺乏CCL20会延迟EAU的分解,并抑制与EAU分解相关的Tregs的诱导(post-EAU Tregs)。重要的是,CCL20缺乏并不影响EAU后treg抑制EAU的能力。这些观察结果的影响是,如果能够绕过阻止眼部treg诱导的缺陷,这些treg仍将能够发挥作用,提供持久的葡萄膜炎缓解。本研究首次证明了及时解决EAU需要CCL20, EAU后Treg的产生需要CCL20,而EAU后Treg抑制疾病不需要CCL20,即及时解决EAU和Treg诱导需要CCL20而不需要CCL20。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
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