Thymosin β4 limits inflammation through autophagy

ABSTRACT

Introduction: Thymosin β4 (Tβ4) is a thymic hormone with multiple and different intracellular and extracellular activities affecting wound healing, inflammation, fibrosis and tissue regeneration. As the failure to resolve inflammation leads to uncontrolled inflammatory pathology which underlies many chronic diseases, the endogenous pathway through which Tβ4 may promote inflammation resolution becomes of great interest. In this review, we discuss data highlighting the efficacy of Tβ4 in resolving inflammation by restoring autophagy.

Areas covered: The authors provide an overview of the Tβ4’s anti-inflammatory properties in several pathologies and provide preliminary evidence on the ability of Tβ4 to resolve inflammation via the promotion of non-canonical autophagy associated with the activation of the DAP kinase anti-inflammatory function.

Expert opinion: Based on its multitasking activity in various animal studies, including tissue repair and prevention of chronic inflammation, Tβ4 may represent a potential, novel treatment for inflammatory diseases associated with defective autophagy.

KEYWORDS:

• Autophagy
• chronic granulomatous disease
• inflammation
• thymosin β4

Declaration of interest

One of the authors A.L. Goldstein is Chairman of the Board & a holder of stock in RegeneRX Biopharmaceuticals, Inc. a company developing Tβ4 for the clinic. The other authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents, received or pending, or royalties.

Article highlights

• Thymosin β4 is a thymus-derived peptide with ever-increasing biological activities in several different types of tissues.

• Thymosin β4 is increasingly being recognized as a molecule endowed with anti-inflammatory activities in different pathologies.

• Autophagy and inflammation are closely intertwined in that impaired autophagy is causally linked to inflammatory pathologies and promoting autophagy favors the resolution of inflammation.

• Thymosin β4 promotes autophagy and ameliorates inflammation in murine and human chronic granulomatous disease upon infection with Aspergillus fumigatus.

This box summarizes key points contained in the article.

Additional information

Funding

This study was supported by the European Research Council (ERC-2011-AdG-293714 to LR). The data contained in this paper were presented at the 5th International Symposium on Thymosins in Health and Disease, Washington DC, USA, November 15–17, 2017.