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Il-23/Th17 cell pathway: A promising target to alleviate thymic inflammation maintenance in myasthenia gravis.
- Source :
-
Journal of autoimmunity [J Autoimmun] 2019 Mar; Vol. 98, pp. 59-73. Date of Electronic Publication: 2018 Dec 18. - Publication Year :
- 2019
-
Abstract
- IL-23/Th17 pathway has been identified to sustain inflammatory condition in several autoimmune diseases and therefore being targeted in various therapeutic and effective approaches. Patients affected with autoimmune myasthenia gravis exhibit a disease effector tissue, the thymus, that harbors ectopic germinal centers that sustain production of auto-antibodies, targeting proteins located in the neuromuscular junction, cause of the organ-specific chronic autoimmune disease. The present study aims to investigate the IL-23/Th17 cell pathway in the thymic inflammatory and pathogenic events. We found that thymuses of MG patients displayed overexpression of Interleukin-17, signature cytokine of activated Th17 cells. This activation was sustained by a higher secretion of Interleukin-23 by TEC, in addition to the increased expression of cytokines involved in Th17 cell development. The overexpression of Interleukin-23 was due to a dysregulation of interferon type I pathway. Besides, Interleukin-17 secreted, and Th17 cells were localized around thymic ectopic germinal centers. These cells expressed podoplanin, a protein involved in B-cell maturation and antibody secretion. Finally, production of Interleukin-23 was also promoted by Interleukin-17 secreted itself by Th17 cells, highlighting a chronic loop of inflammation sustained by thymic cell interaction. Activation of the IL-23/Th17 pathway in the thymus of autoimmune myasthenia gravis patients creates an unstoppable loop of inflammation that may participate in ectopic germinal center maintenance. To alleviate the physio-pathological events in myasthenia gravis patients, this pathway may be considered as a new therapeutic target.<br /> (Copyright © 2018. Published by Elsevier Ltd.)
- Subjects :
- Adolescent
Adult
Cells, Cultured
Child
Child, Preschool
Female
Humans
Infant
Infant, Newborn
Male
Membrane Glycoproteins metabolism
Middle Aged
Signal Transduction
Thymus Gland pathology
Young Adult
Inflammation immunology
Interleukin-17 metabolism
Interleukin-23 metabolism
Myasthenia Gravis immunology
Th17 Cells immunology
Thymus Gland metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9157
- Volume :
- 98
- Database :
- MEDLINE
- Journal :
- Journal of autoimmunity
- Publication Type :
- Academic Journal
- Accession number :
- 30578016
- Full Text :
- https://doi.org/10.1016/j.jaut.2018.11.005