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IL-6 signaling drives self-renewal and alternative activation of adipose tissue macrophages.
Ackermann, Jan; Arndt, Lilli; Fröba, Janine; Lindhorst, Andreas; Glaß, Markus; Kirstein, Michaela; Hobusch, Constance; Wunderlich, F Thomas; Braune, Julia; Gericke, Martin.
Afiliación
  • Ackermann J; Institute of Anatomy, Leipzig University, Leipzig, Germany.
  • Arndt L; Institute of Anatomy and Cell Biology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
  • Fröba J; Institute of Anatomy, Leipzig University, Leipzig, Germany.
  • Lindhorst A; Institute of Anatomy and Cell Biology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
  • Glaß M; Institute of Anatomy, Leipzig University, Leipzig, Germany.
  • Kirstein M; Institute of Anatomy, Leipzig University, Leipzig, Germany.
  • Hobusch C; Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, Charles Tanford Protein Center, Halle (Saale), Germany.
  • Wunderlich FT; Institute of Anatomy and Cell Biology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
  • Braune J; Institute of Anatomy, Leipzig University, Leipzig, Germany.
  • Gericke M; Max-Planck-Institute for Metabolism Research, Research Group for Obesity and Cancer, Cologne, Germany.
Front Immunol ; 15: 1201439, 2024.
Article en En | MEDLINE | ID: mdl-38482013
ABSTRACT

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-6Rα deficiency (Il6ra Δmyel) 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-4Rα knockout mice (Il4ra -/-) we studied IL-6 signaling.

Results:

Obese Il6ra Δmyel 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 Δmyel 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-4Rα axis.

Discussion:

Our results demonstrate IL-4Rα-independent anti-inflammatory effects of IL-6 on macrophages and the ability of IL-6 to maintain proliferation rates in obese AT.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-6 / Diabetes Mellitus Tipo 2 Límite: Animals Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-6 / Diabetes Mellitus Tipo 2 Límite: Animals Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza