Notch and TLR signaling coordinate monocyte cell fate and inflammation.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Limbourg, Florian P
MetadataShow full item record
AbstractConventional Ly6Chi monocytes have developmental plasticity for a spectrum of differentiated phagocytes. Here we show, using conditional deletion strategies in a mouse model of Toll-like receptor (TLR) 7-induced inflammation, that the spectrum of developmental cell fates of Ly6Chi monocytes, and the resultant inflammation, is coordinately regulated by TLR and Notch signaling. Cell-intrinsic Notch2 and TLR7-Myd88 pathways independently and synergistically promote Ly6Clo patrolling monocyte development from Ly6Chi monocytes under inflammatory conditions, while impairment in either signaling axis impairs Ly6Clo monocyte development. At the same time, TLR7 stimulation in the absence of functional Notch2 signaling promotes resident tissue macrophage gene expression signatures in monocytes in the blood and ectopic differentiation of Ly6Chi monocytes into macrophages and dendritic cells, which infiltrate the spleen and major blood vessels and are accompanied by aberrant systemic inflammation. Thus, Notch2 is a master regulator of Ly6Chi monocyte cell fate and inflammation in response to TLR signaling.
CitationElife. 2020 Jul 29;9:e57007. doi: 10.7554/eLife.57007.
AffiliationTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Ly6C<sup>Hi</sup> Blood Monocyte/Macrophage Drive Chronic Inflammation and Impair Wound Healing in Diabetes Mellitus.
- Authors: Kimball A, Schaller M, Joshi A, Davis FM, denDekker A, Boniakowski A, Bermick J, Obi A, Moore B, Henke PK, Kunkel SL, Gallagher KA
- Issue date: 2018 May
- The Cardiac Microenvironment Instructs Divergent Monocyte Fates and Functions in Myocarditis.
- Authors: Hou X, Chen G, Bracamonte-Baran W, Choi HS, Diny NL, Sung J, Hughes D, Won T, Wood MK, Talor MV, Hackam DJ, Klingel K, Davogustto G, Taegtmeyer H, Coppens I, Barin JG, Čiháková D
- Issue date: 2019 Jul 2
- Myeloid <i>Bmal1</i> deletion increases monocyte recruitment and worsens atherosclerosis.
- Authors: Huo M, Huang Y, Qu D, Zhang H, Wong WT, Chawla A, Huang Y, Tian XY
- Issue date: 2017 Mar
- Impaired COMMD10-Mediated Regulation of Ly6C<sup>hi</sup> Monocyte-Driven Inflammation Disrupts Gut Barrier Function.
- Authors: Mouhadeb O, Ben Shlomo S, Cohen K, Farkash I, Gruber S, Maharshak N, Halpern Z, Burstein E, Gluck N, Varol C
- Issue date: 2018
- Spatio-temporal profile, phenotypic diversity, and fate of recruited monocytes into the post-ischemic brain.
- Authors: Garcia-Bonilla L, Faraco G, Moore J, Murphy M, Racchumi G, Srinivasan J, Brea D, Iadecola C, Anrather J
- Issue date: 2016 Nov 4