Interleukin-12p35 deletion promotes CD4 T-cell-dependent macrophage differentiation and enhances angiotensin II-Induced cardiac fibrosis.

Arteriosclerosis, Thrombosis, and Vascular Biology
Yulin LiJie Du

Abstract

Interleukin-12 is essential for the differentiation of naïve T cells into interferon-γ-producing T cells, which regulate inflammatory responses. We investigated this process of regulating hypertension-induced cardiac fibrosis. Mice infused with angiotensin II showed a marked increase in interleukin-12p35 expression in cardiac macrophages. The degree of cardiac fibrosis was significantly enhanced in interleukin-12p35 knockout (p35-KO) mice compared with wild-type (WT) littermates in response to angiotensin II. Fibrotic hearts of p35-KO mice showed increased accumulation of alternatively activated (M2) macrophages and expression of M2 genes such as Arg-1 and Fizz1. Bone marrow-derived macrophages from WT or p35-KO mice did not differ in differentiation in response to angiotensin II treatment; however, in the presence of CD4(+) T cells, macrophages from p35-KO mice differentiated into M2 macrophages and showed elevated expression of transforming growth factor-β. Moreover, CD4(+) T-cell-treated p35-KO macrophages could stimulate cardiac fibroblasts to differentiate into α-smooth muscle actin-positive and collagen I-positive myofibroblasts in 3-dimensional nanofiber gels. Neutralizing antibodies against transforming growth factor-β ...Continue Reading

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Citations

Mar 29, 2014·Cardiovascular Research·Katsuhito FujiuRyozo Nagai
Jan 15, 2014·American Journal of Hypertension·Congcong ZhangJie Du
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Apr 20, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Congcong ZhangJie Du
May 17, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Jie DuXinliang Ma
Dec 26, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Neekun SharmaChetan P Hans
Aug 14, 2020·Genome Génome / Conseil National De Recherches Canada·Hui ZhangYuehong Zheng
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