Restoring T Cell Tolerance, Exploring the Potential of Histone Deacetylase Inhibitors for the Treatment of Juvenile Idiopathic Arthritis

Frontiers in Immunology
Lotte NijhuisJorg van Loosdregt

Abstract

Juvenile Idiopathic Arthritis (JIA) is characterized by a loss of immune tolerance. Here, the balance between the activity of effector T (Teff) cells and regulatory T (Treg) cells is disturbed resulting in chronic inflammation in the joints. Presently, therapeutic strategies are predominantly aimed at suppressing immune activation and pro-inflammatory effector mechanisms, ignoring the opportunity to also promote tolerance by boosting the regulatory side of the immune balance. Histone deacetylases (HDACs) can deacetylate both histone and non-histone proteins and have been demonstrated to modulate epigenetic regulation as well as cellular signaling in various cell types. Importantly, HDACs are potent regulators of both Teff cell and Treg cell function and can thus be regarded as attractive therapeutic targets in chronic inflammatory arthritis. HDAC inhibitors (HDACi) have proven therapeutic potential in the cancer field, and are presently being explored for their potential in the treatment of autoimmune diseases. Specific HDACi have already been demonstrated to reduce the secretion of pro-inflammatory cytokines by Teff cells, and promote Treg numbers and suppressive capacity in vitro and in vivo. In this review, we outline the ro...Continue Reading

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Citations

Apr 3, 2020·International Journal of Molecular Sciences·Andreas von KnethenBernhard Brüne
Jun 21, 2020·International Journal of Molecular Sciences·Sena KimJaebok Choi
Jan 15, 2021·MBio·Jorge Domínguez-AndrésMihai G Netea
Jun 22, 2021·The Journal of Allergy and Clinical Immunology·Cristina Benito-VillalvillaOscar Palomares
Jan 26, 2022·The Australasian Journal of Dermatology·Heba Ahmed AbdelkaderMarwa Ezzat

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Methods Mentioned

BETA
acetylation
histone acetylation

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