Precursors of thymic peptides as stress sensors

ABSTRACT

Introduction

A large volume of data indicates that the known thymic hormones, thymulin, thymopoietin, thymosin-α, thymosin-β, and thymic humoral factor-y2, exhibit different spectra of activities. Although large in volume, available data are rather fragmented, resulting in a lack of understanding of the role played by thymic hormones in immune homeostasis.

Area covered

Existing data compartmentalizes the effect of thymic peptides into 2 categories: influence on immune cells and interconnection with neuroendocrine systems. The current study draws attention to a third aspect of the thymic peptide effect that has not been clarified yet, wherein ubiquitous and highly abundant intranuclear precursors of so called ‘thymic peptides’ play a fundamental role in all somatic cells.

Expert opinion

Our analysis indicated that, under certain stress-related conditions, these precursors are cleaved to form immunologically active peptides that rapidly leave the nucleus and intracellular spaces, to send ‘distress signals’ to the immune system, thereby acting as stress sensors. We propose that these peptides may form a link between somatic cells and immune as well as neuroendocrine systems. This model may provide a better understanding of the mechanisms underlying immune homeostasis, leading thereby to the development of new therapeutic regimes utilizing the characteristics of thymic peptides.

KEYWORDS:

• Apoptosis
• heat shock
• necrosis
• oxidative stress
• thymic hormones
• thymic humoral factor
• thymopoietin
• thymosins thymulin
• tissue damage

Article highlights

• Precursors of thymic hormones are ubiquitous and highly abundant proteins of all somatic cells with nuclear localization and fundamental intracellular functions.

• The precursors are cleaved to form immunologically active peptides and released during early response to stress, to send ‘distress signals’ to the immune system.

• This cleavage may take place in steps, sequentially producing peptide fragments with different immunological effects.

• Thymic peptides may act as a link between somatic cells, immunity, and neuroendocrine systems in order to regulate immune homeostasis.

This box summarizes key points contained in the article.

Acknowledgments

The authors thank Editage for help with language editing.

Declaration of interest

The 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, including employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One of the reviewers of this manuscript owns a patent on the use of Thymosin beta4 in Neurological injury. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

The work was supported by the Russian Foundation for Basic Research [projects No 18-04-00091 and 20-015-00216] and by Russian Academy of Sciences, Program 1.18 ‘Molecular and Cellular Biology and Post-Genomic Technologies’. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.