Neuroimmune Regulation of Atopic Dermatitis
Neuroimmune Regulation of Atopic Dermatitis
批准号:
10544905
负责人:
Brian Kim
金额:
$215.92万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
未结题
起止时间:
2016-08-05 至 2025-08-31
中文摘要
项目摘要/摘要
特应性皮炎(AD)是一种慢性、复发性皮肤病,影响儿童和成人。这种病是一种
日益严重的公共卫生问题和全球巨大的经济负担。最核心的也是最令人衰弱的
阿尔茨海默病的症状是慢性瘙痒。虽然一些患者可以用现有的治疗方法成功地治疗,但有
继续需要开发新的治疗方法来治疗那些对
目前AD的治疗策略。我们和其他人已经证明了2型细胞因子的产生
辅助性T细胞2型(TH2)和新发现的第2组固有淋巴样细胞IL-4和IL-13的表达
(ILC2s)参与AD的发病。初步研究还表明,IL-4和IL-4的受体
13在瘙痒敏感的初级感觉神经元上高表达。然而,TH2细胞的确切作用,
ILC2和2型细胞因子在介导AD相关性瘙痒中的作用仍不明确。此外,2型细胞因子
已知依赖于免疫细胞中的Janus Kinase(JAK)信号来实现其效应功能。
然而,初级感觉神经元中的JAK信号是否会引起瘙痒仍不清楚。中环
这个建议的假设是,特应性瘙痒是由2型免疫细胞之间的相互作用引起的。
和初级感觉神经元通过JAK信号。为了测试这一点,在特定的目标1中,我们将使用基因
改良TH2细胞和/或ILC2缺陷小鼠以研究这些免疫细胞及其相关基因的作用
引起神经元兴奋和瘙痒行为的细胞因子。在具体目标2中,我们将使用依赖于CRE
选择性地从免疫细胞或初级感觉神经元中删除JAK1的条件性基因敲除小鼠
确定感觉神经元特异性JAK信号是否介导瘙痒原诱导的神经元激活
以及瘙痒反应。我们预计,对免疫途径的更好理解
在阿尔茨海默病的背景下,与主要的瘙痒感受器相互作用以促进瘙痒可能导致新的止痒
治疗。
英文摘要
PROJECT SUMMARY/ABSTRACT
Atopic dermatitis (AD) is a chronic, relapsing skin disease that affects children and adults. This disease is a
growing public health problem and a large economic burden worldwide. The central and most debilitating
symptom in AD is chronic itch. While some patients can be treated successfully with existing therapies, there
is a continuing need for the development of new therapies to treat patients who do not respond to
current AD treatment strategies. We and others have shown that the production of the type 2 cytokines
interleukin (IL)-4 and IL-13 by T helper type 2 (TH2) cells and newly identified group 2 innate lymphoid cells
(ILC2s) contribute to AD pathogenesis. Preliminary studies have also shown that the receptors for IL-4 and IL-
13 are highly expressed on itch-sensing primary sensory neurons. However, the precise role of TH2 cells,
ILC2s and type 2 cytokines in mediating AD-associated itch remains poorly defined. Further, type 2 cytokines
are known to be dependent on Janus kinase (JAK) signaling in immune cells for their effector functions.
However, whether JAK signaling in primary sensory neurons elicits itch remains unknown. The central
hypothesis of this proposal is that atopic itch arises from interactions between type 2 immune cells
and primary sensory neurons via JAK signaling. To test this, in Specific Aim 1 we will employ genetically
modified TH2 cell- and/or ILC2-deficient mice to investigate the role of these immune cells and their associated
cytokines in evoking neuronal excitation and itch behavior. In Specific Aim 2, we will employ Cre-dependent
conditional knockout mice in which Jak1 is selectively deleted from immune cells or primary sensory neurons
to determine whether sensory neuron-specific JAK signaling mediates pruritogen-elicited neuronal activation
and itch responses. We anticipate that gaining a better understanding of the immunologic pathways that
interact with the primary pruriceptors to promote itch in the context of AD could lead to new anti-itch
therapies.
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DOI:
10.1016/j.coi.2018.05.005
发表时间:
2018-10
期刊:
Current opinion in immunology
影响因子:
7
作者:
[Trier AM, Kim BS]
通讯作者:
Kim BS
ILC2 require cell-intrinsic ST2 signals to promote type 2 immune responses.
ILC2需要细胞中性ST2信号来促进2型免疫反应。
DOI:
10.3389/fimmu.2023.1130933
发表时间:
2023
期刊:
Frontiers in immunology
影响因子:
7.3
作者:
[]
通讯作者:
DOI:
10.1111/febs.14465
发表时间:
2018-09
期刊:
The FEBS journal
影响因子:
--
作者:
[Oetjen LK, Kim BS]
通讯作者:
Kim BS
DOI:
10.1016/j.it.2018.10.001
发表时间:
2018-12
期刊:
Trends in immunology
影响因子:
16.8
作者:
[Mack MR, Kim BS]
通讯作者:
Kim BS
Treatment of Refractory Chronic Pruritus of Unknown Origin With Tofacitinib in Patients With Rheumatoid Arthritis.
用托法替尼治疗类风湿关节炎患者难治性不明原因的慢性瘙痒。
DOI:
10.1001/jamadermatol.2019.2804
发表时间:
2019
期刊:
JAMA dermatology
影响因子:
10.9
作者:
[Wang,Fang, Morris,Caroline, Bodet,NancyD, Kim,BrianS]
通讯作者:
Kim,BrianS
共 7 条
Research Training in Systems Skin Biology
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批准号:10628103
-
项目类别:
-
资助金额:$18.87万
-
财政年份:2023
-
负责人:Brian Kim
-
依托单位:
Defining the role of IL-18 in atopic dermatitis
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批准号:10681016
-
项目类别:
-
资助金额:$82.43万
-
财政年份:2023
-
负责人:Brian Kim
-
依托单位:
Natural Killer Cell Regulation of Skin Inflammation
-
批准号:10620336
-
项目类别:
-
资助金额:$50.51万
-
财政年份:2022
-
负责人:Brian Kim
-
依托单位:
Natural Killer Cell Regulation of Skin Inflammation
-
批准号:10560030
-
项目类别:
-
资助金额:$50.0万
-
财政年份:2022
-
负责人:Brian Kim
-
依托单位:
The Role of IL-33 in Chronic Itch
-
批准号:10541745
-
项目类别:
-
资助金额:$25.35万
-
财政年份:2021
-
负责人:Brian Kim
-
依托单位:
The Role of IL-33 in Chronic Itch
-
批准号:10495223
-
项目类别:
-
资助金额:$20.7万
-
财政年份:2021
-
负责人:Brian Kim
-
依托单位:
Immune Regulation of Atopic Itch
-
批准号:9326912
-
项目类别:
-
资助金额:$33.55万
-
财政年份:2016
-
负责人:Brian Kim
-
依托单位:
Innate Immune Regulation of Skin Inflammation
-
批准号:8915923
-
项目类别:
-
资助金额:$12.84万
-
财政年份:2014
-
负责人:Brian Kim
-
依托单位:
Innate Immune Regulation of Skin Inflammation
-
批准号:8824491
-
项目类别:
-
资助金额:$12.84万
-
财政年份:2014
-
负责人:Brian Kim
-
依托单位:
海外基金