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[Etude] Le tacrolimus inhibe les réponses Th1 et Th17 chez les patients atteints de myasthénie grave anti-MuSK.

Posté : 13 juin 2019 17:13
par Pboulanger
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:arrow: Lu sur : https://www.ncbi.nlm.nih.gov/pubmed/30472069

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Exp Neurol. 2019 Feb;312:43-50. doi: 10.1016/j.expneurol.2018.11.006. Epub 2018 Nov 22.
Tacrolimus inhibits Th1 and Th17 responses in MuSK-antibody positive myasthenia gravis patients.

Li Y1, Guptill JT2, Russo MA2, Massey JM2, Juel VC2, Hobson-Webb LD2, Howard JF3, Chopra M3, Liu W1, Yi JS4.


Abstract

Muscle specific tyrosine kinase antibody positive myasthenia gravis (MuSK- MG) is characterized by autoantibodies against the MuSK protein of the neuromuscular junction resulting in weakness of bulbar and proximal muscles.

We previously demonstrated that patients with MuSK-MG have increased pro-inflammatory Th1 and Th17 responses.

Tacrolimus, an immunosuppressant used in AChR-MG and transplantation patients, inhibits T cell responses through interference with IL-2 transcription.
The therapeutic efficacy and immunological effect of tacrolimus in MuSK-MG is unclear.

In the current study we examined the proliferation, phenotype and cytokine production of CD4+ and CD8+ T cells in peripheral blood mononuclear cells of MuSK-MG following a 3-day in vitro culture with or without tacrolimus.

We determined that tacrolimus profoundly suppressed CD4 and CD8 T cell proliferation and significantly suppressed Th1 and Th17 responses, as demonstrated by a reduced frequency of IFN-γ, IL-2, and IL-17 producing CD4 T cells and reduced frequencies of IFN-γ and IL-2 producing CD8 T cells.

Tacrolimus also inhibits pathogenic Th17 cells coproducing IL-17 and IFN-γ.

In addition, tacrolimus suppressed follicular T helper cell (Tfh) and regulatory T helper cell (Treg) subsets.

These findings provide preliminary support for tacrolimus as a potential alternative immunosuppressive therapy for MuSK-MG.

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