Sarcoidosis and the mTOR, Rac1, and Autophagy Triad.

Autophagy / genetics Humans Macrophages / immunology Sarcoidosis / genetics TOR Serine-Threonine Kinases / immunology Th1 Cells / immunology Th17 Cells / immunology rac1 GTP-Binding Protein / immunology
Rac1 T cell Treg autophagy azathioprine genetics granuloma mTOR monocyte multinucleated giant cell rapamycin sarcoidosis whole-exome sequencing

Journal

Trends in immunology
ISSN: 1471-4981
Titre abrégé: Trends Immunol
Pays: England
ID NLM: 100966032

Informations de publication

Date de publication:
04 2020
Historique:
received: 29 07 2019
revised: 21 01 2020
accepted: 23 01 2020
pubmed: 4 3 2020
medline: 17 3 2021
entrez: 4 3 2020
Statut: ppublish

Résumé

Sarcoidosis is an enigmatic multisystem disease characterized by the development and accumulation of granulomas: a compact collection of macrophages that have differentiated into epithelioid cells and which are associated with T helper (Th)1 and Th17 cells. Although no single causative factor has been shown to underlie sarcoidosis in humans, its etiology has been related to microbial, environmental, and genetic factors. We examine how these factors play a role in sarcoidosis pathogenesis. Specifically, we propose that dysfunction of mTOR, Rac1, and autophagy-related pathways not only hampers pathogen or nonorganic particle clearance but also participates in T cell and macrophage dysfunction, driving granuloma formation. This concept opens new avenues for potentially treating sarcoidosis and may serve as a blueprint for other granulomatous disorders.

Identifiants

DOI: 10.1016/j.it.2020.01.007 PMID: 32122794
pubmed: 32122794
pii: S1471-4906(20)30017-X
doi: 10.1016/j.it.2020.01.007
pii:
doi:

Substances chimiques

RAC1 protein, human 0
MTOR protein, human EC 2.7.1.1
TOR Serine-Threonine Kinases EC 2.7.11.1
rac1 GTP-Binding Protein EC 3.6.5.2

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

286-299

Subventions

Organisme : Austrian Science Fund FWF
ID : P 27701
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : P 30857
Pays : Austria

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Auteurs

Yves Pacheco (Y)

Inflammation and Immunity of the Respiratory Epithelium - EA7426 (PI3) - South Medical University Hospital - Lyon 1 Claude Bernard University, Pierre-Bénite, France.

Clarice X Lim (CX)

Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.

Thomas Weichhart (T)

Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.

Dominique Valeyre (D)

Department of Pulmonology, Avicenne Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), EA-2363, Université Paris 13, Bobigny, France.

Abderrazzak Bentaher (A)

Inflammation and Immunity of the Respiratory Epithelium - EA7426 (PI3) - South Medical University Hospital - Lyon 1 Claude Bernard University, Pierre-Bénite, France.

Alain Calender (A)

Inflammation and Immunity of the Respiratory Epithelium - EA7426 (PI3) - South Medical University Hospital - Lyon 1 Claude Bernard University, Pierre-Bénite, France; Department of Molecular and Medical Genetics, Hospices Civils de Lyon, University Hospital, Bron, France. Electronic address: alain.calender@chu-lyon.fr.

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Classifications MeSH

Recherchemedicale.com › Phénomènes physiologiques cellulaires › Autophagie › Sarcoidosis and the mTOR, Rac1, and Autophagy Triad.
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Sarcoidosis and the mTOR, Rac1, and Autophagy Triad.
Recherchemedicale.com › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Macrophages › Sarcoidosis and the mTOR, Rac1, and Autophagy Triad.
Recherchemedicale.com › Maladies du système immunitaire › Hypersensibilité › Hypersensibilité retardée › Sarcoïdose › Sarcoidosis and the mTOR, Rac1, and Autophagy Triad.
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Sérine-thréonine kinases TOR › Sarcoidosis and the mTOR, Rac1, and Autophagy Triad.
Recherchemedicale.com › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Sous-populations de lymphocytes T › Lymphocytes T auxiliaires › Lymphocytes auxiliaires Th1 › Sarcoidosis and the mTOR, Rac1, and Autophagy Triad.
Recherchemedicale.com › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Sous-populations de lymphocytes T › Lymphocytes T auxiliaires › Cellules Th17 › Sarcoidosis and the mTOR, Rac1, and Autophagy Triad.
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines G › Protéines G monomériques › Protéines G rho › Protéines G rac › Protéine G rac1 › Sarcoidosis and the mTOR, Rac1, and Autophagy Triad.