PMID- 38482013
OWN - NLM
STAT- MEDLINE
DCOM- 20240315
LR  - 20240318
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 15
DP  - 2024
TI  - IL-6 signaling drives self-renewal and alternative activation of adipose tissue 
      macrophages.
PG  - 1201439
LID - 10.3389/fimmu.2024.1201439 [doi]
LID - 1201439
AB  - INTRODUCTION: Obesity is associated with chronic low-grade inflammation of 
      adipose tissue (AT) and an increase of AT macrophages (ATMs) that is linked to 
      the onset of type 2 diabetes. We have recently shown that neutralization of 
      interleukin (IL)-6 in obese AT organ cultures inhibits proliferation of ATMs, 
      which occurs preferentially in alternatively activated macrophage phenotype. 
      METHODS: In this study, we investigated AT biology and the metabolic phenotype of 
      mice with myeloid cell-specific IL-6Ralpha deficiency (Il6ra (Deltamyel)) after normal 
      chow and 20 weeks of high-fat diet focusing on AT inflammation, ATM polarization 
      and proliferation. Using organotypical AT culture and bone marrow derived 
      macrophages (BMDMs) of IL-4Ralpha knockout mice (Il4ra (-/-)) we studied IL-6 
      signaling. RESULTS: Obese Il6ra (Deltamyel) mice exhibited no differences in insulin 
      sensitivity or histological markers of AT inflammation. Notably, we found a 
      reduction of ATMs expressing the mannose receptor 1 (CD206), as well as a 
      decrease of the proliferation marker Ki67 in ATMs of Il6ra (Deltamyel) mice. 
      Importantly, organotypical AT culture and BMDM data of Il4ra (-/-) mice revealed 
      that IL-6 mediates a shift towards the M2 phenotype independent from the 
      IL-6/IL-4Ralpha axis. DISCUSSION: Our results demonstrate IL-4Ralpha-independent 
      anti-inflammatory effects of IL-6 on macrophages and the ability of IL-6 to 
      maintain proliferation rates in obese AT.
CI  - Copyright (c) 2024 Ackermann, Arndt, Froba, Lindhorst, Glass, Kirstein, Hobusch, 
      Wunderlich, Braune and Gericke.
FAU - Ackermann, Jan
AU  - Ackermann J
AD  - Institute of Anatomy, Leipzig University, Leipzig, Germany.
AD  - Institute of Anatomy and Cell Biology, Martin-Luther-University Halle-Wittenberg, 
      Halle (Saale), Germany.
FAU - Arndt, Lilli
AU  - Arndt L
AD  - Institute of Anatomy, Leipzig University, Leipzig, Germany.
AD  - Institute of Anatomy and Cell Biology, Martin-Luther-University Halle-Wittenberg, 
      Halle (Saale), Germany.
FAU - Froba, Janine
AU  - Froba J
AD  - Institute of Anatomy, Leipzig University, Leipzig, Germany.
FAU - Lindhorst, Andreas
AU  - Lindhorst A
AD  - Institute of Anatomy, Leipzig University, Leipzig, Germany.
FAU - Glass, Markus
AU  - Glass M
AD  - Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, 
      Charles Tanford Protein Center, Halle (Saale), Germany.
FAU - Kirstein, Michaela
AU  - Kirstein M
AD  - Institute of Anatomy and Cell Biology, Martin-Luther-University Halle-Wittenberg, 
      Halle (Saale), Germany.
FAU - Hobusch, Constance
AU  - Hobusch C
AD  - Institute of Anatomy, Leipzig University, Leipzig, Germany.
FAU - Wunderlich, F Thomas
AU  - Wunderlich FT
AD  - Max-Planck-Institute for Metabolism Research, Research Group for Obesity and 
      Cancer, Cologne, Germany.
FAU - Braune, Julia
AU  - Braune J
AD  - Institute of Anatomy, Leipzig University, Leipzig, Germany.
FAU - Gericke, Martin
AU  - Gericke M
AD  - Institute of Anatomy, Leipzig University, Leipzig, Germany.
AD  - Institute of Anatomy and Cell Biology, Martin-Luther-University Halle-Wittenberg, 
      Halle (Saale), Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20240228
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Interleukin-6)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Interleukin-6/metabolism
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - Adipose Tissue/metabolism
MH  - Macrophages/metabolism
MH  - Inflammation/metabolism
MH  - Mice, Knockout
MH  - Obesity/metabolism
PMC - PMC10933059
OTO - NOTNLM
OT  - IL-6
OT  - adipose tissue inflammation
OT  - alternative activation
OT  - diabetes
OT  - macrophages
OT  - mannose receptor
OT  - obesity
OT  - self-renewal
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2024/03/14 06:47
MHDA- 2024/03/15 06:43
PMCR- 2024/01/01
CRDT- 2024/03/14 04:18
PHST- 2023/04/06 00:00 [received]
PHST- 2024/02/13 00:00 [accepted]
PHST- 2024/03/15 06:43 [medline]
PHST- 2024/03/14 06:47 [pubmed]
PHST- 2024/03/14 04:18 [entrez]
PHST- 2024/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2024.1201439 [doi]
PST - epublish
SO  - Front Immunol. 2024 Feb 28;15:1201439. doi: 10.3389/fimmu.2024.1201439. 
      eCollection 2024.