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Autophagy in Autoimmunity

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Front. Immunol. | doi: 10.3389/fimmu.2018.02158

The mitochondrion-lysosome axis in adaptive and innate immunity: Effect of lupus regulator peptide P140 on mitochondria autophagy and NETosis

 Mykolas Bendorius1,  Indira Neeli2, Fengjuan Wang1,  Srinivasa R. Bonam1, Eszter Dombi3, Nelly Buron4, Annie Borgne-Sanchez4, Joanna Poulton3,  Marko Radic2 and  Sylviane MULLER1*
  • 1UMR7242 Biotechnologie et signalisation cellulaire, France
  • 2University of Tennessee Health Science Center, United States
  • 3Nuffield Department of Obstetrics and Gynaecology, Medical Sciences Division, University of Oxford, United Kingdom
  • 4Mitologics SAS, France

Mitochondria deserve special attention as sensors of cellular energy homeostasis and metabolic state. Moreover, mitochondria integrate intra- and extra-cellular signals to determine appropriate cellular responses that range from proliferation to cell death. In autoimmunity, as in other inflammatory chronic disorders, the metabolism of immune cells may be extensively remodeled, perturbing sensitive tolerogenic mechanisms. Here, we examine the distribution and effects of the therapeutic 21-mer peptide called P140, which shows remarkable efficacy in modulating immune responses in inflammatory settings. We measured P140 and control peptide effects on isolated mitochondria, the distribution of peptides in live cells, and their influence on the levels of key autophagy regulators. Our data indicate that while P140 targets macro- and chaperone-mediated autophagy processes, it has little effect, if any, on mitochondria autophagy. Remarkably, however, it suppresses NET release from neutrophils exposed to immobilized NET-anti-DNA IgG complexes. In conjunction, our results suggest that in the mitochondrion-lysosome axis a likely driver of NETosis and inflammation, the P140 peptide does not operate by affecting mitochondria directly.

Keywords: NEtosis, Autophagy, mitochondrion, systemic lupus erythematosus, Neuroinflammation, P140 peptide.

Received: 23 Apr 2018; Accepted: 31 Aug 2018.

Edited by:

Laurence Morel, University of Florida, United States

Reviewed by:

Jason S. Knight, University of Michigan, United States
J. Michelle Kahlenberg, Michigan Medicine, University of Michigan, United States  

Copyright: © 2018 Bendorius, Neeli, Wang, Bonam, Dombi, Buron, Borgne-Sanchez, Poulton, Radic and MULLER. 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: Prof. Sylviane MULLER, UMR7242 Biotechnologie et signalisation cellulaire, Illkirch, France, sylviane.muller@unistra.fr