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Open AccessArticle

Methotrexate Restores CD73 Expression on Th1.17 in Rheumatoid Arthritis and Psoriatic Arthritis Patients and May Contribute to Its Anti-Inflammatory Effect through Ado Production

1
Immunology Department, University of Lyon, Claude Bernard Lyon 1 University, INSERM 1052, CNRS 5286, Cancer Research Center of Lyon (CRCL), Centre Léon Bérard, 69008 Lyon, France
2
Team “Therapeutic Targeting of the Tumor Cells and Their Immune Stroma”, INSERM U1052, CRCL, 69008 Lyon, France
3
Analytical Chemistry Department, ISPB Faculty of Pharmacy, University of Lyon, Claude Bernard Lyon 1 University, 69008 Lyon, France
4
Biochemistry and Toxicology Laboratory, Lyon Sud Hospital, 69310 Pierre-Bénite, France
5
Toxicology Department, ISPB Faculty of Pharmacy, University of Lyon, Claude Bernard Lyon 1 University, 69008 Lyon, France
6
Cytometry Platform, CRCL, 69008 Lyon, France
7
Rheumatology Department, Lyon Sud Hospital, 69310 Pierre-Bénite, France
8
Rheumatology Department, CHU Saint-Etienne,42100 Saint-Etienne, France
9
INSERM U1059, Jean Monnet University, 42100 Saint-Etienne, France
10
INSERM, UMR 1033, Claude Bernard Lyon 1 University, 69008 Lyon, France
*
Author to whom correspondence should be addressed.
Co-last authorship.
J. Clin. Med. 2019, 8(11), 1859; https://doi.org/10.3390/jcm8111859
Received: 29 September 2019 / Revised: 15 October 2019 / Accepted: 29 October 2019 / Published: 3 November 2019
Objectives: Th1.17 are highly polyfunctional, potentially harmful CD4+ effector T cells (Teff) through IFN-γ and IL-17A coproduction. Th1.17 take part in the pathophysiology of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in which their hyper activation results in part from defects in negative regulation mechanisms. We recently demonstrated that the ecto-nucleotidase CD73 delineates a Th1.17-enriched Teff population and acts as an endogenous regulatory mechanism. Because Methotrexate (MTX), used as first line treatment of RA and PsA, increases extracellular concentrations of AMP and immunosuppressive adenosine, we investigated the modulation of CD73 by MTX treatment on Teff in RA/PsA patients. Methods: In a prospective cohort of 26 RA and 15 PsA patients before or under MTX treatment, we evaluated CD73 expression on blood Teff subsets, their cytokine production and AMPase functions. Results: We showed a decreased CD73 expression on Th1.17 and Th1 in untreated patients compared to healthy donors that was partly restored under MTX. This decrease in untreated patients leads to a halved Ado production by Th1.17 cells. CD73+ Teff remained functional under MTX treatment, but their CD73 re-expression may contribute to control their activation. Conclusion: Our study unveils uncovered mode of action of MTX on Teff subsets modulation and in the adenosine-dependent termination of inflammation in RA and PsA.
Keywords: Th1.17; IL-17A; IFN-γ, CD73; adenosine; rheumatoid arthritis; psoriatic arthritis; methotrexate; regulation Th1.17; IL-17A; IFN-γ, CD73; adenosine; rheumatoid arthritis; psoriatic arthritis; methotrexate; regulation
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Bossennec, M.; Rodriguez, C.; Hubert, M.; Di-Roio, A.; Machon, C.; Guitton, J.; Battiston-Montagne, P.; Couturier, M.; Marotte, H.; Caux, C.; Coury, F.; Ménétrier-Caux, C. Methotrexate Restores CD73 Expression on Th1.17 in Rheumatoid Arthritis and Psoriatic Arthritis Patients and May Contribute to Its Anti-Inflammatory Effect through Ado Production. J. Clin. Med. 2019, 8, 1859.

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