Gr-1⁺CD11b⁺ immature myeloid cells (IMC) promote resistance of pro-inflammatory T cells to suppression by regulatory T cells in atherosclerotic Apo E- deficient mice

• Published in: PloS one 2014-09, Vol.9 (9), p.e108620-e108620
• Main Authors: Chen, Yulin, Jian, Ying, Liu, Minjie, Zhong, Liang, Zhang, Fang, Yang, Weifeng, Xu, Zhao, Chen, Guofan, Liu, Yuhua
• Format: Article
• Language: English
• Subjects: Animals; Apolipoproteins; Apolipoproteins E - deficiency; Apolipoproteins E - genetics; Arteriosclerosis; Atherosclerosis; Atherosclerosis - genetics; Atherosclerosis - metabolism; Atherosclerosis - pathology; Autoimmune diseases; Biology and life sciences; Cancer; Cardiology; CD11b antigen; CD11b Antigen - genetics; CD11b Antigen - metabolism; CD4 antigen; Cell activation; Cell Differentiation; Cytokines; Defects; Disease; Disease Progression; Effector cells; Flow cytometry; Gene Expression Regulation; Homeostasis; Hyperactivity; Immunoregulation; Inflammation; Inflammatory diseases; Interleukin 6; Janus Kinases - genetics; Janus Kinases - metabolism; Laboratory animals; Lymphocyte Count; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Myeloid cells; Myeloid Cells - metabolism; Myeloid Cells - pathology; Pathogenesis; Receptors, Chemokine - genetics; Receptors, Chemokine - metabolism; Rodents; Signal Transduction; Signaling; STAT Transcription Factors - genetics; STAT Transcription Factors - metabolism; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - pathology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0108620

Accumulating evidence indicates that both defects in Treg numbers and/or function as well as resistance of effector T cells to suppression may contribute to the development of human chronic inflammatory diseases. However, which mechanism involved in the progression of atherosclerosis remains unclear. In this study, we evaluated the production and function of CD4⁺ inflammatory and regulatory T cells in atherosclerosis-prone mice. We found that the hyperactivity and unresponsiveness to Treg-mediated suppression of inflammatory CD4⁺ T cells occurred in the progression of atherosclerosis, though Treg cells were present in very large numbers and fully functional. We further found that Gr-1⁺CD11b⁺ immature myeloid cells were significantly accumulated in atherosclerotic Apo E⁻/⁻ mice, and they promoted resistance of inflammatory CD4⁺ T cells to Treg-mediated suppression in vitro and in vivo. we further confirmed that Gr-1⁺CD11b⁺ immature myeloid cells produced high level of interleukin 6 which was at least partially responsible for inducing unresponsiveness of inflammatory CD4⁺ T cells to suppression via activation of Jak/Stat signaling pathway. Taken together, these findings might provide new insights to explore potential targets for immune therapeutic intervention in atherosclerosis.