期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 216, 期 2, 页码 369-383出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20180722
关键词
-
资金
- National Institutes of Health [R35 HL135752, R01 HL128264, P01 HL131478, R01 HL111938, R01 HL131006]
- American Heart Association's Established Investigator Award
- Patricia and Scott Eston MGH Research Scholar Award
- Uehara Memorial Foundation
- Kanae Foundation for the Promotion of Medical Science
- Japan Society for the Promotion of Science (KAKENHI) [18K08048]
- Boehringer-Ingelheim Fonds MD fellowship
- American Heart Association postdoctoral fellowship
- Canadian Institutes of Health Research
- Banting Research Foundation
- Fondation pour la Recherche Medicale postdoctoral fellowship
- Grants-in-Aid for Scientific Research [18K08048] Funding Source: KAKEN
Acquisition of self-reactive effector CD4(+) T cells is a major component of the autoimmune response that can occur during myocarditis, an inflammatory form of cardiomyopathy. Although the processes by which self-reactive T cells gain effector function have received considerable attention, how these T cells contribute to effector organ inflammation and damage is less clear. Here, we identified an IL-3-dependent amplification loop that exacerbates autoimmune inflammation. In experimental myocarditis, we show that effector organ-accumulating autoreactive IL-3(+) CD4(+) T cells stimulate IL-3R(+) tissue macrophages to produce monocyte-attracting chemokines. The newly recruited monocytes differentiate into antigen-presenting cells that stimulate local IL-3(+) CD4(+) T cell proliferation, thereby amplifying organ inflammation. Consequently, Il3(-/-) mice resist developing robust autoimmune inflammation and myocardial dysfunction, whereas therapeutic IL-3 targeting ameliorates disease. This study defines a mechanism that orchestrates inflammation in myocarditis, describes a previously unknown function for IL-3, and identifies IL-3 as a potential therapeutic target in patients with myocarditis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据