Self-reactive CD4+ IL-3+ T cells amplify autoimmune inflammation in myocarditis by inciting monocyte chemotaxis

Atsushi Anzai, John E. Mindur, Lennard Halle, Soichi Sano, Jennifer L. Choi, Shun He, Cameron S. McAlpine, Christopher T. Chan, Florian Kahles, Colin Valet, Ashley M. Fenn, Manfred Nairz, Sara Rattik, Yoshiko Iwamoto, De Lisa Fairweather, Kenneth Walsh, Peter Libby, Matthias Nahrendorf, Filip K. Swirski

研究成果: Article

9 引用 (Scopus)

抜粋

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.

元の言語English
ページ(範囲)369-383
ページ数15
ジャーナルJournal of Experimental Medicine
216
発行部数2
DOI
出版物ステータスPublished - 2019 2 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

フィンガープリント Self-reactive CD4<sup>+</sup> IL-3<sup>+</sup> T cells amplify autoimmune inflammation in myocarditis by inciting monocyte chemotaxis' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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    Anzai, A., Mindur, J. E., Halle, L., Sano, S., Choi, J. L., He, S., McAlpine, C. S., Chan, C. T., Kahles, F., Valet, C., Fenn, A. M., Nairz, M., Rattik, S., Iwamoto, Y., Fairweather, D. L., Walsh, K., Libby, P., Nahrendorf, M., & Swirski, F. K. (2019). Self-reactive CD4+ IL-3+ T cells amplify autoimmune inflammation in myocarditis by inciting monocyte chemotaxis. Journal of Experimental Medicine, 216(2), 369-383. https://doi.org/10.1084/jem.20180722