title: 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.
abstract: 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.
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jian
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
authors.forename: Guofan
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D039481:CD11b Antigen / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D018450:Disease Progression; D005786:Gene Expression Regulation; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology*; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000473:pathology*
chemical_list: D001057:Apolipoproteins E; D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine; D050791:STAT Transcription Factors; D053612:Janus Kinases