The Immunoregulatory Enzyme Indoleamine 2,3-Dioxygenase (IDO1) Is Expressed by Natural Killer (NK) Cells During Cytokine-Mediated Activation

吲哚胺2,3-双加氧酶 生物 细胞因子 自然杀伤细胞 白细胞介素12 免疫系统 犬尿氨酸 分子生物学 细胞毒性T细胞 免疫学 生物化学 体外 色氨酸 氨基酸
作者
Cecilia Evangelisti,Antonio Curti,Sara Trabanelli,Darina Očadlíková,Michele Baccarani,Roberto M. Lemoli
出处
期刊:Blood [Elsevier BV]
卷期号:116 (21): 3894-3894
标识
DOI:10.1182/blood.v116.21.3894.3894
摘要

Abstract Abstract 3894 Introduction: human NK cells are large, granular cells derived from lymphocyte lineage. They are critical mediators of the innate immunity as they rapidly respond to pathogens infected and tumour cells through cytotoxic and cytokines-producing responses. Indoleamine 2,3-dioxygenase (IDO1) is an enzyme catalyzing the degradation of the essential amino acid L-tryptophan into kynurenines. Several cell types, including dendritic cells, have been shown to express IDO1, which acts as a potent immunosuppressive agent. Recently, in addiction to IDO1, the new variant IDO2 was described but its immunosuppressive role is still under investigations. The aim of the present work is to study the expression and the role of IDO1 and IDO2 in NK cells. Methods: CD3-CD56+NK cells were immunomagnetically purified from healthy donors. IFN-gamma production was measured by ELISA assay. IDO1 and DAP12 transcript levels were normalized on ABL. IDO2 expression was measured by semi-quantitative PCR. Kynurenine levels were evaluated by colorimetric assay. Results: peripheral blood NK cells were treated with IL-2 for 16h, 40h, 88h and 160h. At the end of each IL-2 stimulation, supernatants were collected and IFN-gamma production was measured by colorimetric assay. IDO1 expression in NK cells was evaluated by quantitative real-time PCR and Western blotting. Our data show that, during IL-2-mediated activation, IDO1 is up-regulated at mRNA and protein levels. This effect is maximum after an overnight incubation and it decreases at later time points. IDO1 expression is clearly correlated with IFN-gamma production by NK cells whereas IFN-gamma receptor expression is not affected. Culturing NK cells with a combination of IL-2 and anti-IFN-gamma antibody demonstrated that IDO1 expression is regulated, at least in part, by IFN-gamma. Interestingly, IDO1 mRNA upregulation is associated with downregulation of DAP12, a gene whose expression has been showed to be inversely correlated to IDO1 in dendritic cells. IDO2 expression seems to be not affected by IL-2 stimulation. Treatment with other inflammatory cytokines demonstrated that IDO1 is modulated by different stimuli. Overnight incubation with IL-12, IFN-gamma and a combination of IL-2 and IL-6 showed IDO1 induction. IFN-gamma showed the highest IDO1 induction at transcript and protein level and, surprisingly, of IDO2 expression. IDO1 expression by NK cells resulted in increased production of kynurenines and this effect was abrogated by the addition of the IDO1 inhibitor 1-methyl tryptophan. Conclusion: our results demonstrate that NK cells upregulate IDO1 expression during cytokine-mediated activation and that IDO1 expression is regulated, at least in part, by IFN-gamma. Similarly to DCs, NK cells express IDO1 gene in association with DAP12, thus suggesting a common regulatory pathway among different cell subsets. Disclosures: Baccarani: NOVARTIS: Honoraria; BRISTOL MYERS SQUIBB: Honoraria.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
公西翠萱完成签到 ,获得积分10
刚刚
qixiaoqi发布了新的文献求助10
1秒前
博慧完成签到 ,获得积分10
2秒前
小刘医生完成签到,获得积分10
4秒前
安安完成签到,获得积分10
4秒前
啊啊啊啊完成签到,获得积分10
4秒前
英俊的铭应助飞飞鱼采纳,获得10
6秒前
科目三应助zzz采纳,获得10
6秒前
小小西瓜萝卜青菜完成签到,获得积分10
6秒前
思源应助虚幻采枫采纳,获得10
7秒前
7秒前
不安的可乐完成签到,获得积分10
7秒前
8秒前
nano完成签到 ,获得积分10
8秒前
da完成签到,获得积分10
8秒前
科研通AI2S应助啊啊啊啊采纳,获得10
9秒前
cyndi发布了新的文献求助20
9秒前
10秒前
852应助小小西瓜萝卜青菜采纳,获得10
12秒前
sci完成签到,获得积分10
13秒前
醉熏的鑫发布了新的文献求助10
14秒前
Nizarn发布了新的文献求助10
14秒前
15秒前
15秒前
乐呵呵完成签到,获得积分10
15秒前
15秒前
忧心的惜天完成签到 ,获得积分10
15秒前
77完成签到,获得积分10
16秒前
yz发布了新的文献求助10
16秒前
周周南完成签到 ,获得积分10
19秒前
19秒前
zz完成签到,获得积分10
19秒前
自由老头应助cyndi采纳,获得20
20秒前
努力做实验完成签到 ,获得积分10
21秒前
wf发布了新的文献求助10
21秒前
研友_ngkEgn完成签到,获得积分10
21秒前
代丽娟完成签到,获得积分10
21秒前
23秒前
快来下载文献完成签到,获得积分10
23秒前
苹果山芙完成签到,获得积分10
24秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds第二卷 1200
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038657
求助须知:如何正确求助?哪些是违规求助? 3576306
关于积分的说明 11375198
捐赠科研通 3306108
什么是DOI,文献DOI怎么找? 1819379
邀请新用户注册赠送积分活动 892698
科研通“疑难数据库(出版商)”最低求助积分说明 815066