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J Autoimmun. 2016 Dec;75:82-95. doi: 10.1016/j.jaut.2016.07.009. Epub 2016 Jul 30.

Symbiotic gut commensal bacteria act as host cathepsin S activity regulators.

Author information

1
Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany.
2
Institute of Radiology, Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, University of Tübingen, Tübingen, Germany.
3
Department of Clinical Reasearch, Gastroenterology, University of Bern, Bern, Switzerland.
4
Interfacultary Institute of Biochemistry, Universitiy of Tübingen, Tübingen, Germany.
5
Institute of Medical Microbiology and Hygiene, University of Tübingen, Tübingen, Germany. Electronic address: julia-stefanie.frick@med.uni-tuebingen.de.

Abstract

Cathepsin S (CTSS) is a lysosomal protease whose activity regulation is important for MHC-II signaling and subsequent activation of CD4+ T cell mediated immune responses. Dysregulation of its enzymatic activity or enhanced secretion into extracellular environments is associated with the induction or progression of several autoimmune diseases. Here we demonstrate that commensal intestinal bacteria influence secretion rates and intracellular activity of host CTSS and that symbiotic bacteria, i.e. Bacteroides vulgatus mpk, may actively regulate this process and help to maintain physiological levels of CTSS activities in order to prevent from induction of pathological inflammation. The symbiont-controlled regulation of CTSS activity is mediated by anticipating reactive oxygen species induction in dendritic cells which, in turn, maintains cystatin C (CysC) monomer binding to CTSS. CysC monomers are potent endogenous CTSS inhibitors. This Bacteroides vulgatus caused and CysC dependent CTSS activity regulation is involved in the generation of tolerant intestinal dendritic cells contributing to prevention of T-cell mediated induction of colonic inflammation. Taken together, we demonstrate that symbionts of the intestinal microbiota regulate host CTSS activity and secretion and might therefore be an attractive approach to deal with CTSS associated autoimmune diseases.

KEYWORDS:

Autoimmune disease; Cathepsin S; Immunotherapy; Inflammatory bowel disease; Microbiota; Protease regulation

PMID:
27484364
DOI:
10.1016/j.jaut.2016.07.009
[Indexed for MEDLINE]

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