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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Neurosci. | doi: 10.3389/fncel.2019.00430

Loss of IL-10 promotes differentiation of microglia to a M1 phenotype

 Björn Laffer1, 2,  Dirk Bauer1,  Susanne Wasmuth1, Martin Busch1, Tida V. Jalilvand1, 3, Solon Thanos3,  Gerd Meyer Zu Horste4,  Karin Loser5,  Thomas Langmann6, Arnd Heiligenhaus1, 7 and  Maren Kasper1*
  • 1Department of Ophthalmology and Ophtha-Lab, St. Franziskus Hospital, Germany
  • 2Department of Ophthalmology, University Hospital Essen, Germany
  • 3Institute of Experimental Ophthalmology, University Münster, Germany
  • 4Department of Neurology, University Hospital Münster, Germany
  • 5Department of General Dermatology, University Hospital Münster, Germany
  • 6Department of Ophthalmology, University Hospital Cologne, Germany
  • 7University of Duisburg-Essen, Germany

Microglia represent the primary resident immune cells of the central nervous system (CNS) and modulate local immune responses. Depending on their physiological functions, microglia can be classified into pro- (M1) and anti-inflammatory (M2) phenotype. Interleukin (IL)-10 is an important modulator of neuronal homeostasis, with anti-inflammatory and neuroprotective functions, and can be released by microglia. Here, we investigated how IL-10 deficiency affected the M1/2 polarization of primary microglia upon lipopolysaccharide (LPS) stimulation in vitro. Microglia phenotypes were analyzed via flow cytometry. Cytokine and chemokine secretion were examined by ELISA and bead-based multiplex LEGENDplex™. Our results showed that genetic depletion of IL-10 led to elevated M1 like phenotype (CD86+CD206-) under pro-inflammatory conditions associated with increased frequency of IL-6+, TNF-α+ cells and enhanced release of several pro-inflammatory chemokines. Absence of IL-10 led to an attenuated M2 like phenotype (CD86-CD206+) and a reduced secretion of TGF-β1 upon LPS stimulation. In conclusion, IL-10 deficiency may promote the polarisation of microglia into M1-prone phenotype under pro-inflammatory conditions.

Keywords: Cytokines, Microglia, M1/M2 polarization, LPS (lipopolysaccharide), IL-10 (interleukin-10), phenotype

Received: 22 May 2019; Accepted: 09 Sep 2019.

Copyright: © 2019 Laffer, Bauer, Wasmuth, Busch, Jalilvand, Thanos, Meyer Zu Horste, Loser, Langmann, Heiligenhaus and Kasper. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Maren Kasper, Department of Ophthalmology and Ophtha-Lab, St. Franziskus Hospital, Münster, Germany, maren.kasper@uveitis-zentrum.de