Thymosin α1: burying secrets in the thymus

Abstract

Thymosin α1 (Tα1), an epithelial cell (EC)-derived cytokine, has the strong ability to modulate signals delivered through innate immune receptors on dendritic cells (DCs), thus instructing the initiation of appropriate immune responses to T cells. In its ability to activate indoleamine 2,3-dioxygenase 1-dependent tolerogenic programs in DCs, Tα1 pivotally contributes to the maintenance of self-tolerance by regulating the function of regulatory T (Treg) cells. How Tα1 may contribute to the Treg cell ontogeny is not known. The transcriptional regulator autoimmune regulator (AIRE) is known to control central and peripheral tolerance. AIRE is highly expressed in thymic medullary ECs where it controls the ectopic expression of tissue restricted antigens for negative selection. The absence of AIRE-induced tissue-specific antigens in the thymus can lead to autoimmunity in the antigen-expressing target organ. Recently, AIRE protein has been detected in peripheral lymphoid organs, suggesting that peripheral AIRE may play a complementary role. We have addressed the possible relationship between AIRE and Tα1 and discovered an intricate crosstalk, whereby AIRE may promote prothymosin cleavage to Tα1, and Tα1 in turn transcriptionally regulates AIRE expression. Thus, similar to other members of thymic stromal poietins, Tα1 expressed within the thymus and peripheral tissues regulates the EC/DC crosstalk required for salutary immune homeostasis.

Keywords:

• autoimmune regulator
• indoleamine 2,3-dioxygenase
• immune tolerance
• thymosin α1

Acknowledgment

The authors thank Dr Cristina Massi Benedetti for digital art and editing.

Declaration of interest

This paper is part of a supplemental issue, sponsored by SciClone. The research in this paper was supported by the Specific Targeted Research Project FunMeta (ERC-2011-AdG-293714) to L Romani. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents, received or pending, or royalties.

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