Self-reactive CD4+ IL-3+ T cells amplify autoimmune inflammation in myocarditis by inciting monocyte chemotaxis.
J Exp Med
; 216(2): 369-383, 2019 02 04.
Article
en En
| MEDLINE
| ID: mdl-30670465
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Autoinmunes
/
Monocitos
/
Linfocitos T CD4-Positivos
/
Quimiotaxis
/
Interleucina-3
/
Miocarditis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Exp Med
Año:
2019
Tipo del documento:
Article
País de afiliación:
Marruecos