Lu sur : https://www.ncbi.nlm.nih.gov/pubmed/30578016
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J Autoimmun. 2018 Dec 18. pii: S0896-8411(18)30607-3. doi: 10.1016/j.jaut.2018.11.005. [Epub ahead of print]
Il-23/Th17 cell pathway: A promising target to alleviate thymic inflammation maintenance in myasthenia gravis.
Villegas JA1, Bayer AC1, Ider K1, Bismuth J1, Truffault F1, Roussin R2, Santelmo N3, Le Panse R4, Berrih-Aknin S1, Dragin N5.
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.
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