PMID- 32619089
OWN - NLM
STAT- MEDLINE
DCOM- 20210621
LR  - 20210621
IS  - 2055-5822 (Electronic)
IS  - 2055-5822 (Linking)
VI  - 7
IP  - 5
DP  - 2020 Oct
TI  - Characterization of dendritic cells in human and experimental myocarditis.
PG  - 2305-2317
LID - 10.1002/ehf2.12767 [doi]
AB  - AIMS: Dendritic cells (DCs) are central mediators of adaptive immunity, and there 
      is growing evidence of their role in myocardial inflammatory disease. We 
      hypothesized that plasmacytoid and myeloid DCs are involved in the mechanisms of 
      myocarditis and analysed these two main subtypes in human myocarditis subjects, 
      as well as in a murine model of experimental autoimmune myocarditis (EAM). 
      METHODS AND RESULTS: Circulating DCs were analysed by flow cytometry in patients 
      with acute myocarditis, dilated cardiomyopathy, and controls. Myocardial biopsies 
      were immunostained for the presence of DCs and compared with non-diseased 
      controls. In a mouse model of acute myocarditis induced through synthetic cardiac 
      myosine peptide injection, effects of immunomodulation including DC inhibition 
      through MCS-18 versus placebo treatment were tested at the peak of inflammation 
      (Day 21), as well as 1 week later (partial recovery). Circulatory pDCs and mDCs 
      were significantly reduced in myocarditis patients compared with controls (P < 
      0.01 for both) and remained so even after 6 months of follow-up. Human 
      myocarditis biopsies showed accumulation of pDCs (two-fold CD304+/three-fold 
      CD123+, all P < 0.05) compared with controls. Myocardial pDCs and mDCs 
      accumulated in EAM (P for both <0.0001). MCS-18 treatment reduced pDC levels (P = 
      0.009), reduced myocardial inflammation (myocarditis score reduction from 2.6 to 
      1.8, P = 0.026), and improved ejection fraction (P = 0.03) in EAM at Day 21 (peak 
      of inflammation). This effect was not observed during the partial recovery of 
      inflammation on Day 28. CONCLUSIONS: Circulating DCs are reduced in human 
      myocarditis and accumulate in the inflamed myocardium. MCS-18 treatment reduces 
      DCs in EAM, leading to amelioration of inflammation and left ventricular 
      remodelling during the acute phase of myocarditis. Our data further elucidate the 
      role of DCs and their specific subsets in acute inflammatory cardiomyopathies.
CI  - (c) 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on 
      behalf of the European Society of Cardiology.
FAU - Pistulli, Rudin
AU  - Pistulli R
AUID- ORCID: 0000-0001-7676-3942
AD  - Department of Cardiology I - Coronary and Peripheral Vascular Disease, Heart 
      Failure, University Hospital Munster, Albert-Schweitzer-Campus 1, Gebaude A1, 
      Munster, 48149, Germany.
FAU - Andreas, Elise
AU  - Andreas E
AD  - Department of Internal Medicine I, Division of Cardiology, University Hospital 
      Jena, Jena, Germany.
FAU - Konig, Sebastian
AU  - Konig S
AD  - Heart Center Leipzig, Leipzig, Germany.
FAU - Drobnik, Stefanie
AU  - Drobnik S
AD  - Institute of Forensic Medicine, University of Jena, Jena, Germany.
FAU - Kretzschmar, Daniel
AU  - Kretzschmar D
AD  - Department of Internal Medicine I, Division of Cardiology, University Hospital 
      Jena, Jena, Germany.
FAU - Rohm, Ilonka
AU  - Rohm I
AD  - Department of Internal Medicine I, Division of Cardiology, University Hospital 
      Jena, Jena, Germany.
FAU - Lichtenauer, Michael
AU  - Lichtenauer M
AD  - Department of Cardiology, University of Salzburg, Salzburg, Austria.
FAU - Heidecker, Bettina
AU  - Heidecker B
AD  - Department of Cardiology, Charite Universitatsmedizin Berlin, Campus Benjamin 
      Franklin, Berlin, Germany.
FAU - Franz, Marcus
AU  - Franz M
AD  - Department of Internal Medicine I, Division of Cardiology, University Hospital 
      Jena, Jena, Germany.
FAU - Mall, Gita
AU  - Mall G
AD  - Institute of Forensic Medicine, University of Jena, Jena, Germany.
FAU - Yilmaz, Atilla
AU  - Yilmaz A
AD  - Internal Medicine Clinic II, Elisabeth Hospital, Schmalkalden, Germany.
FAU - Schulze, P Christian
AU  - Schulze PC
AD  - Department of Internal Medicine I, Division of Cardiology, University Hospital 
      Jena, Jena, Germany.
LA  - eng
GR  - Else-Kroner-Fresenius Foundation (PCS)/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200703
PL  - England
TA  - ESC Heart Fail
JT  - ESC heart failure
JID - 101669191
SB  - IM
MH  - Animals
MH  - *Cardiomyopathy, Dilated
MH  - Dendritic Cells
MH  - Humans
MH  - Inflammation
MH  - Mice
MH  - *Myocarditis
MH  - Myocardium
PMC - PMC7524053
OTO - NOTNLM
OT  - Dendritic cell
OT  - Dilated cardiomyopathy
OT  - Experimental autoimmune myocarditis
OT  - Heart failure
OT  - Myocarditis
COIS- None declared.
EDAT- 2020/07/04 06:00
MHDA- 2021/06/22 06:00
PMCR- 2020/07/03
CRDT- 2020/07/04 06:00
PHST- 2019/08/21 00:00 [received]
PHST- 2020/04/22 00:00 [revised]
PHST- 2020/05/04 00:00 [accepted]
PHST- 2020/07/04 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/07/04 06:00 [entrez]
PHST- 2020/07/03 00:00 [pmc-release]
AID - EHF212767 [pii]
AID - 10.1002/ehf2.12767 [doi]
PST - ppublish
SO  - ESC Heart Fail. 2020 Oct;7(5):2305-2317. doi: 10.1002/ehf2.12767. Epub 2020 Jul 
      3.