LPS and type I and II interferons have opposing effects on epigenetic regulation of LAIR1 expression in mouse and human macrophages

生物 转录因子 免疫系统 染色质 雷布 染色质免疫沉淀 干扰素调节因子 林恩 表观遗传学 基因表达 肿瘤坏死因子α 基因表达调控 细胞生物学 转录调控 分子生物学 免疫学 NFKB1型 先天免疫系统 基因 信号转导 遗传学 发起人 酪氨酸激酶
作者
Hannah K Dorando,Evan C Mutic,J Li,Elizabeth Perrin,Mellisa Wurtz,Chaz Quinn,Jacqueline E. Payton
出处
期刊:Journal of Leukocyte Biology [Wiley]
卷期号:115 (3): 547-564
标识
DOI:10.1093/jleuko/qiad148
摘要

Inhibitory immune receptors are important for maintaining immune homeostasis. We identified epigenetic alterations in 2 members of this group, LAIR1 and LAIR2, in lymphoma patients with inflammatory tissue damage and susceptibility to infection. We predicted that the expression of LAIR genes is controlled by immune mediators acting on transcriptional regulatory elements. Using flow cytometry, quantitative reverse-transcription polymerase chain reaction, and RNA sequencing, we measured LAIR1 and LAIR2 in human and murine immune cell subsets at baseline and posttreatment with immune mediators, including type I and II interferons, tumor necrosis factor α, and lipopolysaccharide (LPS). We identified candidate regulatory elements using epigenome profiling and measured their regulatory activity using luciferase reporters. LAIR1 expression substantially increases during monocyte differentiation to macrophages in both species. In contrast, murine and human macrophages exhibited opposite changes in LAIR1 in response to immune stimuli: human LAIR1 increased with LPS while mouse LAIR1 increased with interferon γ. LAIR genes had distinct patterns of enhancer activity with variable responses to immune stimuli. To identify relevant transcription factors (TFs), we developed integrative bioinformatic techniques applied to TF chromatin immunoprecipitation sequencing, RNA sequencing, and luciferase activity, revealing distinct sets of TFs for each LAIR gene. Most strikingly, LAIR1 TFs include nuclear factor kappa B factors RELA and RELB, while Lair1 and LAIR2 instead include STAT3 and/or STAT5. Regulation by nuclear factor kappa B factors may therefore explain the LPS-induced increase in LAIR1 expression, in contrast to Lair1 decrease. Our findings reveal new insights into transcriptional mechanisms that control distinct expression patterns of LAIR genes in response to inflammatory stimuli in human and murine myeloid and lymphoid cells.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

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
Ava应助北林采纳,获得30
刚刚
Morgans00完成签到,获得积分10
刚刚
刚刚
刚刚
1秒前
2秒前
自然秋柳发布了新的文献求助10
2秒前
雪.发布了新的文献求助10
2秒前
GZM应助阿门采纳,获得10
2秒前
优美谷兰发布了新的文献求助10
2秒前
西瓜完成签到,获得积分20
3秒前
3秒前
麻瓜小羊完成签到,获得积分10
3秒前
英姑应助动听乐珍采纳,获得30
3秒前
欢喜的早晨完成签到,获得积分10
4秒前
shjyang发布了新的文献求助10
4秒前
雪白笑南完成签到,获得积分10
5秒前
CodeCraft应助WonderHua采纳,获得10
5秒前
慕觅云发布了新的文献求助30
5秒前
复杂大象完成签到,获得积分10
5秒前
Wen发布了新的文献求助10
5秒前
小二郎应助卿卿采纳,获得10
6秒前
pluto应助太阳采纳,获得10
7秒前
7秒前
月月发布了新的文献求助10
7秒前
软绵绵完成签到,获得积分10
7秒前
cctv18应助hh0采纳,获得10
7秒前
所所应助木叶_卡卡西采纳,获得10
7秒前
淡淡十三发布了新的文献求助10
8秒前
8秒前
8秒前
失眠翎完成签到,获得积分20
9秒前
Solarenergy发布了新的文献求助30
10秒前
10秒前
兜里没糖发布了新的文献求助10
10秒前
小猫最受完成签到,获得积分10
10秒前
bkagyin应助pan采纳,获得10
10秒前
11秒前
失眠的霸完成签到,获得积分10
11秒前
科研通AI2S应助优美谷兰采纳,获得10
12秒前
高分求助中
The late Devonian Standard Conodont Zonation 2000
The Lali Section: An Excellent Reference Section for Upper - Devonian in South China 1500
Nickel superalloy market size, share, growth, trends, and forecast 2023-2030 1000
Smart but Scattered: The Revolutionary Executive Skills Approach to Helping Kids Reach Their Potential (第二版) 1000
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 800
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 800
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 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 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3245398
求助须知:如何正确求助?哪些是违规求助? 2889057
关于积分的说明 8256709
捐赠科研通 2557392
什么是DOI,文献DOI怎么找? 1386090
科研通“疑难数据库(出版商)”最低求助积分说明 650285
邀请新用户注册赠送积分活动 626541